Thrombin or factor Xa inhibitors

ABSTRACT

This invention relates generally to inhibitors of trypsin-like serine protease enzymes, especially factor Xa or thrombin, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.

This application claims the benefit of U.S. Provisional Application No. 60/113627, filed Dec. 23, 1998.

FIELD OF THE INVENTION

This invention relates generally to inhibitors of trypsin-like serine protease enzymes, especially factor Xa or thrombin, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.

BACKGROUND OF THE INVENTION

Activated factor Xa, whose major practical role is the generation of thrombin by the limited proteolysis of prothrombin, holds a central position that links the intrinsic and extrinsic activation mechanisms in the final common pathway of blood coagulation. The generation of thrombin, the final serine protease in the pathway to generate a fibrin clot, from its precursor is amplified by formation of prothrombinase complex (factor Xa, factor V, Ca²⁺ and phospholipid). Since it is calculated that one molecule of factor Xa can generate 138 molecules of thrombin (Elodi, S., Varadi, K.: Optimization of conditions for the catalytic effect of the factor IXa-factor VIII Complex: Probable role of the complex in the amplification of blood coagulation. Thromb. Res. 1979, 15, 617-629), inhibition of factor Xa may be more efficient than inactivation of thrombin in interrupting the blood coagulation system.

Therefore, efficacious and specific inhibitors of factor Xa, thrombin, or both are needed as potentially valuable therapeutic agents for the treatment of thromboembolic disorders. It is thus desirable to discover new factor Xa, thrombin, or both inhibitors.

SUMMARY OF THE INVENTION

Accordingly, one object of the present invention is to provide novel nitrogen containing aromatic heterocycles, with ortho-substituted P1 groups, which are useful as factor Xa inhibitors or pharmaceutically acceptable salts or prodrugs thereof.

It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.

It is another object of the present invention to provide a method for treating thromboembolic disorders comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.

It is another object of the present invention to provide novel compounds for use in therapy.

It is another object of the present invention to provide the use of novel compounds for the manufacture of a medicament for the treatment of thrombosis or a disease mediated by factor Xa.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[1] Thus, in an embodiment, the present invention provides a novel compound selected from the group:

ring D is selected from —(CH₂)₃—, —CH₂CH═CH—, —CH₂N═CH—, and a 5 membered aromatic system containing from 0-2 heteroatoms selected from the group N, O, and S, provided that from 0-1 O and S atoms are present;

ring D is substituted with 0-2 R;

E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, substituted with 0-1R;

R is selected from Cl, F, Br, I, OH, C₁₋₃ alkoxy, NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂, CH₂CH₂NH₂, CH₂CH₂NH(C₁₋₃ alkyl), and CH₂CH₂N(C₁₋₃ alkyl)₂;

M is selected from the group:

J is O or S;

J^(a) is NH or NR^(1a);

Z is selected from (CR⁸R⁹)₁₋₄, (CR⁸R⁹)_(r)O(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)O(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)OC(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³C(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)OC(O)O(CR⁸R⁹)_(r), (CH₂)_(r)OC(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³C(O)O(CR⁸R⁹)_(r), (CH₂)_(r)NR³C(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)S(O)_(p)(CR⁸R⁹)_(r), (CCR⁸R⁹)_(r)SO₂NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³SO₂(CR⁸R⁹)_(r), and (CR⁸R⁹)_(r)NR³SO₂NR³(CR⁸R⁹)_(r), provided that Z does not form a N—N, N—O, N—S, NCH₂N, NCH₂O, or NCH₂S bond with the groups to which Z is attached;

R^(1a) is selected from H, —(CH₂)_(r)—R^(1′), —CH═CH—R^(1′), NHCH₂R^(1″), OCH₂R^(1″), SCH₂R^(1″), NH(CH₂)₂(CH₂)_(t)R^(1′), O(CH₂)₂(CH₂)_(t)R^(1′), and S(CH₂)₂(CH₂)_(t)R^(1′);

R^(1′) is selected from H, C₁₋₃ alkyl, F, Cl, Br, I, —CN, —CHO, (CF₂)_(r)CF₃, (CH₂)_(r)OR², NR²R^(2a), C(O)R^(2c), OC(O)R², (CF₂)_(r)CO₂R^(2c), S(O)_(p)R^(2b), NR²(CH₂)_(r)OR², C(═NR^(2C))NR²R^(2a), NR²C(O)R^(2b), NR²C(O)NHR^(2b), NR²C(O)₂R^(2a), OC(O)NR^(2a)R^(2b), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR², SO₂NR²R^(2a), NR²SO₂R^(2b), C₃₋₆ carbocyclic residue substituted with 0-2 R⁴, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R⁴;

R^(1″) is selected from H, CH(CH₂OR²)₂, C(O)R^(2c), C(O)NR²R^(2a), S(O)R^(2b), S(O)₂R^(2b), and SO₂NR²R^(2a);

R², at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocyclic residue substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b);

R^(2a), at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl, benzyl, C₃₋₆ cycloalkylmethyl substituted with 0-2 R^(4b), C₃₋₆ carbocyclic residue substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b);

R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxy, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocyclic residue substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b);

R^(2c), at each occurrence, is selected from CF₃, OH, C₁₋₄ alkoxy, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocyclic residue substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b);

alternatively, R² and R^(2a) combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R^(4b) which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;

alternatively, R² and R^(2a), together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R^(4b) and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;

R³, at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl;

R^(3a), at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl;

R^(3b), at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl;

R^(3c), at each occurrence, is selected from C₁₋₄ alkyl, and phenyl;

A is selected from:

C₃₋₁₀ carbocyclic residue substituted with 0-2 R⁴, and

5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R⁴;

B is selected from:

X-Y, NR²R^(2a), C(═NR²)NR²R^(2a), NR²C(═NR²)NR²R^(2a),

C₃₋₁₀ carbocyclic residue substituted with 0-2 R^(4a), and

5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a);

X is selected from C₁₋₄ alkylene, —CR²(CR²R^(2b))(CH₂)_(t)—, —C(O)—, —C(═NR^(1″))—, —CR²(NR^(1″)R²)—, —CR²(OR²)—, —CR²(SR²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —S(O)_(p)—, —S(O)_(p)CR²R^(2a)—, —CR²R^(2a)S(O)_(p)—, —S(O)₂NR²—, —NR²S(O)₂—, —NR²S(O)₂CR²R^(2a)—, —CR²R^(2a)S(O)₂NR²—, —NR²S(O)₂NR²—, —C(O)NR²—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—, —CR²R^(2a)NR²(O)—, —NR²C(O)O—, —OC(O)NR²—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —CR²R^(2a)O—, and OCR²R^(2a)—;

Y is selected from:

(CH₂)_(r)NR²R^(2a), provided that X-Y do not form a N—N, O—N, or S—N bond,

C₃₋₁₀ carbocyclic residue substituted with 0-2 R^(4a), and

5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a);

R⁴, at each occurrence, is selected from H, ═O, (CH₂)_(r)OR², F, Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), NR²C(O)NR²R^(2a), C(═NR²)NR²R^(2a), C(═NS(O)₂R⁵)NR²R^(2a), NHC(═NR²)NR²R^(2a), C(O)NHC(═NR²)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂—C₁₋₄ alkyl, NR²SO₂R⁵, S(O)_(p)R⁵, (CF₂)_(r)CF₃, NHCH₂R^(1″), OCHR^(1″), SCH₂R^(1″), N(CH₂)₂(CH₂)_(t)R^(1′), O(CH₂)₂(CH₂)_(t)R^(1′), and S(CH₂)₂(CH₂)_(t)R^(1′),

alternatively, one R⁴ is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S;

R^(4a), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR², (CH₂)_(r)—F, (CH₂)_(r)—Br, (CH₂)_(r)— Cl, Cl, Br, F, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), C(O)NH(CH₂)₂NR²R^(2a), NR²C(O)NR²R^(2a), C(═NR²)NR²R^(2a)NHC(═NR²)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂—C₁₋₄ alkyl, C(O)NHSO₂—C₁₋₄ alkyl, NR²SO₂R⁵, S(O)_(p)R⁵, and (CF₂)_(r)CF₃;

alternatively, one R^(4a) is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-1 R⁵;

R^(4b), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR³, F, Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³, (CH₂)_(r)C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), NR³C(O)NR³R^(3a), C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂— phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, and (CF₂)_(r)CF₃;

R⁵, at each occurrence, is selected from CF₃, C₁₋₆ alkyl, phenyl substituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶;

R⁶, at each occurrence, is selected from H, OH, (CH₂)_(r)OR², halo, C₁₋₄ alkyl, CN, NO₂, (CH₂)_(r)NR²R^(2a),(CH₂)_(r)C(O)R^(2b), NR²C(O)R^(2b), NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a), NR²SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl;

R⁷, at each occurrence, is selected from H, OH, C₁₋₆ alkyl, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxy, C₁₋₄ alkoxycarbonyl, (CH₂)_(n)-phenyl, C₆₋₁₀ aryloxy, C₆₋₁₀ aryloxycarbonyl, C₆₋₁₀ arylmethylcarbonyl, C₁₋₄ alkylcarbonyloxy C₁₋₄ alkoxycarbonyl, C₆₋₁₀ arylcarbonyloxy C₁₋₄ alkoxycarbonyl, C₁₋₆ alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C₁₋₄ alkoxycarbonyl;

R⁸, at each occurrence, is selected from H, C₁₋₆ alkyl and (CH₂)_(n)-phenyl;

alternatively, R⁷ and R⁸ combine to form a 5 or 6 membered saturated, ring which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;

R⁹, at each occurrence, is selected from H, C₁₋₆ alkyl and (CH₂)_(n)-phenyl;

n, at each occurrence, is selected from 0, 1, 2, and 3;

m, at each occurrence, is selected from 0, 1, and 2;

p, at each occurrence, is selected from 0, 1, and 2;

r, at each occurrence, is selected from 0, 1, 2, and 3;

s, at each occurrence, is selected from 0, 1, and 2; and,

t, at each occurrence, is selected from 0, 1, 2, and 3.

[2] In another embodiment, the present invention provides a novel compound selected from the group:

wherein, M is selected from the group:

R is selected from H, Cl, F, Br, I, (CH₂)_(t)OR³, C₁₋₄ alkyl, OCF₃, CF₃, C(O)NR⁷R⁸, and (CR⁸R⁹)_(t)NR⁷R⁸;

Z is selected from CH₂O, OCH₂, CH₂NH, NHCH₂, C(O), CH₂C(O), C(O)CH₂, NHC(O), C(O)NH, CH₂S(O)₂, S(O)₂(CH₂), SO₂NH, and NHSO₂, provided that Z does not form a N—N, N—O, NCH₂N, or NCH₂O bond with ring M or group A;

A is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R⁴;

phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl;

B is selected from: H, Y, and X-Y;

X is selected from C₁₋₄ alkylene, —C(O)—, —C(═NR)—, —CR²(NR²R^(2a))—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —C(O)NR²—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—, —CR²R^(2a)NR²C(O)—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—;

Y is NR²R^(2a) or CH₂NR²R^(2a), provided that X-Y do not form a N—N or O—N bond;

alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R^(4a);

cylcopropyl, cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl;

alternatively, Y is selected from the following bicyclic heteroaryl ring systems:

K is selected from O, S, NH, and N.

[3] In another embodiment, the present invention provides a novel compound selected from the group:

M is selected from the group:

Z is C(O)CH₂ and CONH, provided that Z does not form a N—N bond with group A;

A is selected from phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2 R⁴; and,

B is selected from Y, X-Y, phenyl, pyrrolidino, morpholino, 1,2,3-triazolyl, and imidazolyl, and is substituted with 0-1 R^(4a);

B is selected from: Y and X-Y;

X is selected from CH₂, —C(O)—, and O;

Y is NR²R^(2a) or CH₂NR²R^(2a), provided that X-Y does not form an O—N bond;

alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R^(4a);

phenyl, piperazinyl, pyridyl, pyrimidyl, morpholinyl, pyrrolidinyl, imidazolyl, and 1,2,3-triazolyl;

R², at each occurrence, is selected from H, CF₃, CH₃, benzyl, and phenyl;

R^(2a), at each occurrence, is selected from H, CF₃, CH₃, CH(CH₃)₂, cyclopropylmethyl, benzyl, and phenyl;

alternatively, R² and R^(2a) combine to form a ring system substituted with 0-2 R^(4b), the ring system being selected from pyrrolidinyl, piperazinyl and morpholino;

R⁴, at each occurrence, is selected from OH, (CH₂)_(r)OR², Cl, F, C₁₋₄ alkyl, (CH₂)_(r)NR²R^(2a), and (CF₂)_(r)CF₃;

R^(4a) is selected from Cl, F, C₁₋₄ alkyl, CF₃, (CH₂)_(r)NR²R^(2a), S(O)_(p)R⁵, SO₂NR²R^(2a), and 1-CF₃-tetrazol-2-yl;

R^(4b), at each occurrence, is selected from OH, Cl, F, CH₃, and CF₃;

R⁵, at each occurrence, is selected from CF₃, C₁₋₆ alkyl, phenyl, and benzyl;

R⁷, at each occurrence, is selected from H, CH₃, and CH₂CH₃; and,

R⁸, at each occurrence, is selected from H and CH₃.

[4] In another embodiment, the present invention provides a novel compound wherein:

M is selected from the group:

J is N;

R^(1a) is absent or is —(CH₂)_(r)—R^(1′);

R^(1′) is selected from H, C₁₋₃ alkyl, F, Cl, —CN, CF₃, (CH₂)_(r)OR², NR²R^(2a), C(O)R^(2c), OC(O)R², S(O)_(p)R^(2b), NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a), C₃₋₆ carbocyclic residue substituted with 0-2 R^(4a), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a);

A is selected from the group: phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl; and,

B is selected from the group: 2-CF₃-phenyl, 2-(aminosulfonyl)phenyl, 2-(methylaminosulfonyl)phenyl, 2-(dimethylaminosulfonyl)phenyl, 1-pyrrolidinocarbonyl, 2-(methylsulfonyl)phenyl, 2-(N,N-dimethylaminomethyl)phenyl, 2-(isopropylaminomethyl)phenyl, 2-(cyclopropylaminomethyl)phenyl, 2-(N-pyrrolidinylmethyl)phenyl, 2-(3-hydroxy-N-pyrrolidinylmethyl)phenyl, 4-morpholino, 2-(1′-CF₃-tetrazol-2-yl)phenyl, 4-morpholinocarbonyl, 1-methyl-2-imidazolyl, 2-methyl-1-imidazolyl, 5-methyl-1-imidazolyl, 2-(N,N-dimethylaminomethyl)imidazolyl, 2-methylsulfonyl-1-imidazolyl and, 5-methyl-1,2,3-triazolyl.

In another embodiment, the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of present invention or a pharmaceutically acceptable salt form thereof.

In another embodiment, the present invention provides a novel method for treating or preventing a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt form thereof.

DEFINITIONS

The compounds herein described may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins, C═N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated. All processes used to prepare compounds of the present invention and intermediates made therein are considered to be part of the present invention.

“Substituted” is intended to indicate that one or more hydrogens on the atom indicated in the expression using “substituted” is replaced with a selection from the indicated group(s), provided that the indicated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., ═O) group, then 2 hydrogens on the atom are replaced.

The present invention is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium. Isotopes of carbon include C-13 and C-14.

When any variable (e.g., R⁶) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R⁶, then said group may optionally be substituted with up to two R⁶ groups and R⁶ at each occurrence is selected independently from the definition of R⁶. Also, combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.

When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom on the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such substituent. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.

As used herein, “alkyl” or “alkylene” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. C₁₋₁₀ alkyl (or alkylene), is intended to include C₁, C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, and C₁₀ alkyl groups. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl. “Haloalkyl” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more halogen (for example —C_(v)F_(w) where v=1 to 3 and w=1 to (2v+1)). Examples of haloalkyl include, but are not limited to, trifluoromethyl, trichloromethyl, pentafluoroethyl, and pentachloroethyl. “Alkoxy” represents an alkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge. C₁₋₁₀ alkoxy, is intended to include C₁, C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, and C₁₀ alkoxy groups. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy. “Cycloalkyl” is intended to include saturated ring groups, such as cyclopropyl, cyclobutyl, or cyclopentyl. C₃₋₇ cycloalkyl, is intended to include C₃, C₄, C₅, C₆, and C₇ cycloalkyl groups. “Alkenyl” or “alkenylene” is intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon—carbon bonds which may occur in any stable point along the chain, such as ethenyl and propenyl. C₂₋₁₀ alkenyl (or alkenylene), is intended to include C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, and C₁₀ alkenyl groups. “Alkynyl” or “alkynylene” is intended to include hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain, such as ethynyl and propynyl. C₂₋₁₀ alkynyl (or alkynylene), is intended to include C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, and C₁₀ alkynyl groups.

“Halo” or “halogen” as used herein refers to fluoro, chloro, bromo, and iodo; and “counterion” is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, and sulfate.

As used herein, “carbocycle” or “carbocyclic group” is intended to mean any stable 3, 4, 5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, 10, 11, 12, or 13-membered bicyclic or tricyclic, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, and tetrahydronaphthyl.

As used herein, the term “heterocycle” or “heterocyclic group” is intended to mean a stable 5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, or 10-membered bicyclic heterocyclic ring which is saturated, partially unsaturated or unsaturated (aromatic), and which consists of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, NH, O and S and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. A nitrogen in the heterocycle may optionally be quatemized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1. As used herein, the term “aromatic heterocyclic group” or “heteroaryl” is intended to mean a stable 5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, or 10-membered bicyclic heterocyclic aromatic ring which consists of carbon atoms and 1, 2, 3, or 4 heterotams independently selected from the group consisting of N, NH, O and S. It is to be noted that total number of S and O atoms in the aromatic heterocycle is not more than 1.

Examples of heterocycles include, but are not limited to, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl. Also included are fused ring and Spiro compounds containing, for example, the above heterocycles.

The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, filmaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.

The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the disclosure of which is hereby incorporated by reference.

“Prodrugs” are intended to include any covalently bonded carriers which release the active parent drug according to formula (I) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of a compound of formula (I) are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of formula (I) wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug or compound of formula (I) is administered to a mammalian subject, cleaves to form a free hydroxyl, free amino, or free sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of formula (I), and the like.

“Stable compound” and “stable structure” are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

“Therapeutically effective amount” is intended to include an amount of a compound of the present invention or an amount of the combination of compounds claimed effective to inhibit factor Xa or thrombin or treat diseases related to factor Xa or thrombin in a host. The combination of compounds is preferably a synergistic combination. Synergy, as described for example by Chou and Talalay, Adv. Enzyme Regul. 22:27-55 (1984), occurs when the effect (in this case, inhibition of factor Xa or thrombin) of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at suboptimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased antiviral effect, or some other beneficial effect of the combination compared with the individual components.

SYNTHESIS

The compounds of the present invention can be prepared in a number of ways known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or by variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those described below. The reactions are performed in a solvent appropriate to the reagents and materials employed and suitable for the transformations being effected. It will be understood by those skilled in the art of organic synthesis that the functionality present on the molecule should be consistent with the transformations proposed. This will sometimes require a judgment to modify the order of the synthetic steps or to select one particular process scheme over another in order to obtain a desired compound of the invention. It will also be recognized that another major consideration in the planning of any synthetic route in this field is the judicious choice of the protecting group used for protection of the reactive functional groups present in the compounds described in this invention. An authoritative account describing the many alternatives to the trained practitioner is Greene and Wuts (Protective Groups In Organic Synthesis, Wiley and Sons, 1991). All references cited herein are hereby incorporated in their entirety herein by reference.

Compounds wherein rings D-E are A or B, shown below:

can be prepared via the methodology outlined in Scheme I below.

Removal of the amino protecting group followed by further manipulation can afford key starting materials wherein the amino is a benzylamine or alpha-amino acid or all analogs stated earlier. The starting material can also be obtained from intermediate 4 via an SN2 type displacement of the o-tosylate. Decarboxylation of intermediate 3 affords the ketone analog that also can be further manipulated to afford additional starting materials D-E. Coupling of analogs such as intermediate 7 via standard techniques followed by displacement of the phenoxy pyridine via standard techniques known to those in the art should afford the compounds of formula A. Chiral compounds can be separated via chiral HPLC techniques or by co-crystallization methods with a known chiral precursor.

Compounds wherein D-E is of formula B as shown above can be prepared as shown in Scheme II.

Via this scheme amino intermediates such as 3(B) and phenoxy analogs 6 and 7 can be obtained easily via the methods previously described. These intermediates can be further coupled to requisite precursors followed by conversion of the phenoxy group to an amino via standard techniques to afford the amino-pyridyl compounds of formula 1-3.

The unsaturated analogs can be prepared according to Scheme III.

Intermediate 3 can be further manipulated to afford other D-E intermediates via methods described previously. In a similar fashion the other unsaturated analog can be prepared via Scheme IV shown below.

Scheme V describes the preparation of 3-aminobenzofuran intermediates.

4-benzyloxy-2(1H)-pyridone (available from Aldrich) can be converted to the aminopyridine derivative using standard procedures known to the practitioners of the art. Debenzylation, coupling with bromoethylacetate, followed by basic hydrolysis affords an intermediate that undergoes the Friedel-Crafts acylation.

Scheme VI describes the preparation of indole intermediates.

Scheme VII describes the preparation of 3-halo-4-aminobenzothiophene intermediates.

Scheme VIII describes the preparation of 1-substituted-7-amino-azabenzimidazole intermediates.

Scheme X describes the preparation of 2-substituted-7-amino-azabenzimidazole intermediates.

Scheme XI describes the preparation of 5-aminobenzisoxazole intermediates.

Synthesis of 5-aminobenzisoxazoles in which the 3-position may be a protected amine could be accomplished starting from the commercially available 3-cyano-4-fluoronitrobenzene. Displacement of flourine with acetohydroxamic acid under basic conditions followed by ring closure by subsequent addition to the nitrile would yield the benzisoxazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XII describes the preparation of 5-aminoindazole intermediates.

Synthesis of 5-aminoindazoles in which the 3-position may be a protected amine could be accomplished starting from the commercially available 3-cyano-4-fluoronitrobenzene. Displacement of flourine with hydrazine followed by ring closure by subsequent addition to the nitrile would yield the indazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XIII describes the preparation of 5-aminobenzisothiazole intermediates.

Synthesis of 5-aminobenzisothiazoles in which the 3-position may be a protected amine could be accomplished starting from the commercially available 2-benzylthio-5-nitrobenzonitrile. Conversion of the aryl nitrile to benzamidine, sulfoxide formation and ring closure/debenzylation would yield the benzisothiazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XIV describes the preparation of 6-aminobenzisoxazoleintermediates.

Synthesis of 6-aminobenzisoxazoles in which the 3-position may be a protected amine could be accomplished starting from commercially available 2-fluoro-4-nitrobenzoic acid. Conversion of carboxylic acid to nitrile via standard manipulations would give 2-fluoro-4-nitrobenzonitrile. Displacement of flourine with acetohydroxamic acid under basic conditions followed by ring closure by subsequent addition to the nitrile would yield the benzisoxazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XV describes the preparation of 5-aminoindazole intermediates.

Synthesis of 5-aminoindazoles in which the 3-position may be a protected amine could be accomplished starting from 2-fluoro-4-nitrobenzonitrile whose synthesis is described elsewhere in this patent. Displacement of flourine with hydrazine followed by ring closure by subsequent addition to the nitrile would yield the indazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XVI describes the preparation of 6-aminobenzisothiazole intermediates.

Synthesis of 6-aminobenzisothiazoles in which the 3-position may be a protected amine could be accomplished starting from 2-fluoro-4-nitrobenzonitrile whose synthesis is described elsewhere in this patent. Displacement of flourine with benzylthio anion yields 2-benzylthio-4-nitrobenzonitrile. Conversion of the aryl nitrile to benzamidine, sulfoxide formation and ring closure/debenzylation would yield the benzisothiazole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XVII describes the preparation of 6-aminoisoindole intermediates.

Synthesis of 6-aminoisoindoles in which the 1-position may be a protected amine could be accomplished starting from commercially available 2-cyano-4-nitrotoluene. Bromination of tolyl methyl to give a benzyl bromide followed by displacement with azide and reduction to benzylamine would cyclize to the isoindole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XVIII describes the preparation of 5-aminoisoindole intermediates.

Synthesis of 5-aminoisoindoles in which the 1-position may be a protected amine could be accomplished starting from commercially available 2-cyano-5-nitrotoluene. Bromination of tolyl methyl to give a benzyl bromide followed by displacement with azide and reduction to benzylamine would cyclize to the isoindole core. Suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XIX describes the preparation of 2-aminoindole derivatives a intermediates.

Synthesis of the desired compounds in which the 4-position may be a protected amine could be accomplished starting from the commercially available furan or thiophene. Using literature methods (J. Med. Chem. 1989, 32, 1147) one could obtain the 2-nitro-4-chloro-furo or thieno<3,2-c>pyridine. Displacement of the 4-chloro with phenoxide then conversion to 4-amino followed by suitable protection and reduction of the aryl nitro group would provide the desired compound.

Scheme XX describes the preparation of 2-amino-1-H-pyrrolo[3,2-c]pyridine intermediates.

Synthesis of 2-amino-1-H -pyrrolo[3,2-c]pyridine in which the 4-position may be a protected amine could be accomplished starting from the commercially available pyrrole-2-carboxaldehyde. Nitration and protection of pyrrole nitrogen with P1 would afford the nitro/aldehyde intermediate. Using literature methods (J. Med. Chem. 1989, 32, 1147) one could obtain the 2-nitro-4-chloro-pyrrolo[3,2-c]pyridine. Displacement of the 4-chloro with phenoxide then conversion to 4-amino followed by suitable protection and reduction of the aryl nitro group would provide the desired compound.

BOC-Protected aminobenzisoxazolemethylbromide can be reacted with the lithium salt of acetonitrile to give the nitrile. The nitrile can be further reacted in a similar fashion as in WO96/16940 to give the desired compound.

The compounds of the present invention have a group “A-B” attached to ring M. Preparations of some of the rings M and the “A-B” moieties can follow the same methods described in WO97/23212, WO97/30971, WO97/38984, WO98/01428, WO98/06694, WO98/28269, WO98/28282, WO98/57934, WO98/57937, and WO98/57951, the contents of which are incorporated herein by reference. Preparations of the some of the rings M can also follow the same methods described in WO98/28269, WO98/5795 1, and WO98/57937, the contents of which are incorporated herein by reference. Compounds of Formula I can be prepared by reacting an appropriate 6-5 system described above with an appropriate intermediate to either form the desired ring M or to be attached to desired ring M. The above noted publications describe conditions for coupling ring M and a desired 6-5 system.

Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments which are given for illustration of the invention and are not intended to be limiting thereof.

Utility

The compounds of this invention are useful as anticoagulants for the treatment or prevention of thromboembolic disorders in mammals. The term “thromboembolic disorders” as used herein includes arterial or venous cardiovascular or cerebrovascular thromboembolic disorders, including, for example, unstable angina, first or recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary and cerebral arterial thrombosis, cerebral embolism, kidney embolisms, and pulmonary embolisms. The anticoagulant effect of compounds of the present invention is believed to be due to inhibition of factor Xa, thrombin, or both.

The effectiveness of compounds of the present invention as inhibitors of factor Xa can be determined using purified human factor Xa and synthetic substrate. The rate of factor Xa hydrolysis of chromogenic substrate S2222 (Kabi Pharmacia, Franklin, Ohio) can be measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA, which can be monitored spectrophotometrically by measuring the increase in absorbance at 405 nM. A decrease in the rate of absorbance change at 405 nm in the presence of inhibitor is indicative of enzyme inhibition. The results of this assay are expressed as inhibitory constant, K_(i).

Factor Xa determinations were made in 0.10 M sodium phosphate buffer, pH 7.5, containing 0.20 M NaCl, and 0.5% PEG 8000. The Michaelis constant, K_(m), for substrate hydrolysis can be determined at 25° C. using the method of Lineweaver and Burk. Values of K_(i) were determined by allowing 0.2-0.5 nM human factor Xa (Enzyme Research Laboratories, South Bend, Ind.) to react with the substrate (0.20 mM-1 mM) in the presence of inhibitor. Reactions were allowed to go for 30 minutes and the velocities (rate of absorbance change vs time) were measured in the time frame of 25-30 minutes. The following relationship can be used to calculate K_(i) values:

(v_(o)−v_(s))/v_(s)=I/(K_(i)(1+S/K_(m)))

where:

v_(o) is the velocity of the control in the absence of inhibitor;

v_(s) is the velocity in the presence of inhibitor;

I is the concentration of inhibitor;

K_(i) is the dissociation constant of the enzyme:inhibitor complex;

S is the concentration of substrate;

K_(m) is the Michaelis constant.

Compounds tested in the above assay are considered to be active if they exhibit a K_(i) of ≦10 μM. Preferred compounds of the present invention have K_(i)'s of ≦1 μM. More preferred compounds of the present invention have K_(i)'s of ≦0.1 μM. Even more preferred compounds of the present invention have K_(i)'s of ≦0.01 μM. Still more preferred compounds of the present invention have K_(i)'s of ≦0.001 μM.

The antithrombotic effect of compounds of the present invention can be demonstrated in a rabbit arterio-venous (AV) shunt thrombosis model. In this model, rabbits weighing 2-3 kg anesthetized with a mixture of xylazine (10 mg/kg i.m.) and ketamine (50 mg/kg i.m.) are used. A saline-filled AV shunt device is connected between the femoral arterial and the femoral venous cannulae. The AV shunt device consists of a piece of 6-cm tygon tubing which contains a piece of silk thread. Blood will flow from the femoral artery via the AV-shunt into the femoral vein. The exposure of flowing blood to a silk thread will induce the formation of a significant thrombus. After forty minutes, the shunt is disconnected and the silk thread covered with thrombus is weighed. Test agents or vehicle will be given (i.v., i.p., s.c., or orally) prior to the opening of the AV shunt. The percentage inhibition of thrombus formation is determined for each treatment group. The ID50 values (dose which produces 50% inhibition of thrombus formation) are estimated by linear regression.

The compounds of formula (I) may also be useful as inhibitors of serine proteases, notably human thrombin, plasma kallikrein and plasmin. Because of their inhibitory action, these compounds are indicated for use in the prevention or treatment of physiological reactions, blood coagulation and inflammation, catalyzed by the aforesaid class of enzymes. Specifically, the compounds have utility as drugs for the treatment of diseases arising from elevated thrombin activity such as myocardial infarction, and as reagents used as anticoagulants in the processing of blood to plasma for diagnostic and other commercial purposes.

Compounds of the present invention can be shown to be direct acting inhibitors of the serine protease thrombin by their ability to inhibit the cleavage of small molecule substrates by thrombin in a purified system. In vitro inhibition constants were determined by the method described by Kettner et al. in J. Biol. Chem. 265, 18289-18297 (1990), herein incorporated by reference. In these assays, thrombin-mediated hydrolysis of the chromogenic substrate S2238 (Helena Laboratories, Beaumont, Tex.) can be monitored spectrophotometrically. Addition of an inhibitor to the assay mixture results in decreased absorbance and is indicative of thrombin inhibition. Human thrombin (Enzyme Research Laboratories, Inc., South Bend, Ind.) at a concentration of 0.2 nM in 0.10 M sodium phosphate buffer, pH 7.5, 0.20 M NaCl, and 0.5% PEG 6000, can be incubated with various substrate concentrations ranging from 0.20 to 0.02 mM. After 25 to 30 minutes of incubation, thrombin activity can be assayed by monitoring the rate of increase in absorbance at 405 nm which arises owing to substrate hydrolysis. Inhibition constants were derived from reciprocal plots of the reaction velocity as a function of substrate concentration using the standard method of Lineweaver and Burk.

Compounds tested in the above assay are considered to be active if they exhibit a K_(i) of ≦10 μM. Preferred compounds of the present invention have K_(i)'s of ≦1 μM. More preferred compounds of the present invention have K_(i)'s of ≦0.1 μM. Even more preferred compounds of the present invention have K_(i)'s of ≦0.01 μM. Still more preferred compounds of the present invention have K_(i)'s of ≦0.001 μM.

The compounds of the present invention can be administered alone or in combination with one or more additional therapeutic agents. These include other anti-coagulant or coagulation inhibitory agents, anti-platelet or platelet inhibitory agents, thrombin inhibitors, or thrombolytic or fibrinolytic agents.

The compounds are administered to a mammal in a therapeutically effective amount. By “therapeutically effective amount” it is meant an amount of a compound of Formula I that, when administered alone or in combination with an additional therapeutic agent to a mammal, is effective to prevent or ameliorate the thromboembolic disease condition or the progression of the disease.

By “administered in combination” or “combination therapy” it is meant that the compound of Formula I and one or more additional therapeutic agents are administered concurrently to the mammal being treated. When administered in combination each component may be administered at the same time or sequentially in any order at different points in time. Thus, each component may be administered separately but sufficiently closely in time so as to provide the desired therapeutic effect. Other anticoagulant agents (or coagulation inhibitory agents) that may be used in combination with the compounds of this invention include warfarin and heparin, as well as other factor Xa inhibitors such as those described in the publications identified above under Background of the Invention.

The term anti-platelet agents (or platelet inhibitory agents), as used herein, denotes agents that inhibit platelet function such as by inhibiting the aggregation, adhesion or granular secretion of platelets. Such agents include, but are not limited to, the various known non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, sulindac, indomethacin, mefenamate, droxicam, diclofenac, sulfinpyrazone, and piroxicam, including pharmaceutically acceptable salts or prodrugs thereof. Of the NSAIDS, aspirin (acetylsalicyclic acid or ASA), and piroxicam are preferred. Other suitable anti-platelet agents include ticlopidine, including pharmaceutically acceptable salts or prodrugs thereof. Ticlopidine is also a preferred compound since it is known to be gentle on the gastro-intestinal tract in use. Still other suitable platelet inhibitory agents include IIb/IIIa antagonists, thromboxane-A2-receptor antagonists and thromboxane-A2-synthetase inhibitors, as well as pharmaceutically acceptable salts or prodrugs thereof.

The term thrombin inhibitors (or anti-thrombin agents), as used herein, denotes inhibitors of the serine protease thrombin. By inhibiting thrombin, various thrombin-mediated processes, such as thrombin-mediated platelet activation (that is, for example, the aggregation of platelets, and/or the granular secretion of plasminogen activator inhibitor-1 and/or serotonin) and/or fibrin formation are disrupted. A number of thrombin inhibitors are known to one of skill in the art and these inhibitors are contemplated to be used in combination with the present compounds. Such inhibitors include, but are not limited to, boroarginine derivatives, boropeptides, heparins, hirudin and argatroban, including pharmaceutically acceptable salts and prodrugs thereof.

Boroarginine derivatives and boropeptides include N-acetyl and peptide derivatives of boronic acid, such as C-terminal a-aminoboronic acid derivatives of lysine, omithine, arginine, homoarginine and corresponding isothiouronium analogs thereof. The term hirudin, as used herein, includes suitable derivatives or analogs of hirudin, referred to herein as hirulogs, such as disulfatohirudin. Boropeptide thrombin inhibitors include compounds described in Kettner et al., U.S. Pat. No. 5,187,157 and EP 293 881 A2, the disclosures of which are hereby incorporated herein by reference. Other suitable boroarginine derivatives and boropeptide thrombin inhibitors include those disclosed in WO92/07869 and EP 471,651 A2, the disclosures of which are hereby incorporated herein by reference.

The term thrombolytics (or fibrinolytic) agents (or thrombolytics or fibrinolytics), as used herein, denotes agents that lyse blood clots (thrombi). Such agents include tissue plasminogen activator, anistreplase, urokinase or streptokinase, including pharmaceutically acceptable salts or prodrugs thereof. The term anistreplase, as used herein, refers to anisoylated plasminogen streptokinase activator complex, as described, for example, in European Patent Application No. 028,489, the disclosure of which is hereby incorporated herein by reference herein. The term urokinase, as used herein, is intended to denote both dual and single chain urokinase, the latter also being referred to herein as prourokinase.

Administration of the compounds of Formula I of the invention in combination with such additional therapeutic agent, may afford an efficacy advantage over the compounds and agents alone, and may do so while permitting the use of lower doses of each. A lower dosage minimizes the potential of side effects, thereby providing an increased margin of safety.

The compounds of the present invention are also useful as standard or reference compounds, for example as a quality standard or control, in tests or assays involving the inhibition of factor Xa. Such compounds may be provided in a commercial kit, for example, for use in pharmaceutical research involving factor Xa. For example, a compound of the present invention could be used as a reference in an assay to compare its known activity to a compound with an unknown activity. This would ensure the experimenter that the assay was being performed properly and provide a basis for comparison, especially if the test compound was a derivative of the reference compound. When developing new assays or protocols, compounds according to the present invention could be used to test their effectiveness.

The compounds of the present invention may also be used in diagnostic assays involving factor Xa. For example, the presence of factor Xa in an unknown sample could be determined by addition of chromogenic substrate S2222 to a series of solutions containing test sample and optionally one of the compounds of the present invention. If production of pNA is observed in the solutions containing test sample, but not in the presence of a compound of the present invention, then one would conclude factor Xa was present.

Dosage and Formulation

The compounds of this invention can be administered in such oral dosage forms as tablets, capsules (each of which includes sustained release or timed release formulations), pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions. They may also be administered in intravenous (bolus or infusion), intraperitoneal, subcutaneous, or intramuscular form, all using dosage forms well known to those of ordinary skill in the pharmaceutical arts. They can be administered alone, but generally will be administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice.

The dosage regimen for the compounds of the present invention will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the species, age, sex, health, medical condition, and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; the route of administration, the renal and hepatic function of the patient, and the effect desired. A physician or veterinarian can determine and prescribe the effective amount of the drug required to prevent, counter, or arrest the progress of the thromboembolic disorder.

By way of general guidance, the daily oral dosage of each active ingredient, when used for the indicated effects, will range between about 0.001 to 1000 mg/kg of body weight, preferably between about 0.01 to 100 mg/kg of body weight per day, and most preferably between about 1.0 to 20 mg/kg/day. Intravenously, the most preferred doses will range from about 1 to about 10 mg/kg/minute during a constant rate infusion. Compounds of this invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three, or four times daily.

Compounds of this invention can be administered in intranasal form via topical use of suitable intranasal vehicles, or via transdermal routes, using transdermal skin patches. When administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittent throughout the dosage regimen.

The compounds are typically administered in admixture with suitable pharmaceutical diluents, excipients, or carriers (collectively referred to herein as pharmaceutical carriers) suitably selected with respect to the intended form of administration, that is, oral tablets, capsules, elixirs, syrups and the like, and consistent with conventional pharmaceutical practices.

For instance, for oral administration in the form of a tablet or capsule, the active drug component can be combined with an oral, non-toxic, pharmaceutically acceptable, inert carrier such as lactose, starch, sucrose, glucose, methyl callulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like; for oral administration in liquid form, the oral drug components can be combined with any oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Moreover, when desired or necessary, suitable binders, lubricants, disintegrating agents, and coloring agents can also be incorporated into the mixture. Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth, or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

The compounds of the present invention can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines.

Compounds of the present invention may also be coupled with soluble polymers as targetable drug carriers. Such polymers can include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylaspartamidephenol, or polyethyleneoxide-polylysine substituted with palmitoyl residues. Furthermore, the compounds of the present invention may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, and crosslinked or amphipathic block copolymers of hydrogels.

Dosage forms (pharmaceutical compositions) suitable for administration may contain from about 1 milligram to about 100 milligrams of active ingredient per dosage unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition.

Gelatin capsules may contain the active ingredient and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract.

Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance.

In general, water, a suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, buffer substances. Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium EDTA. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.

Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, a standard reference text in this field.

Representative useful pharmaceutical dosage-forms for administration of the compounds of this invention can be illustrated as follows:

Capsules

A large number of unit capsules can be prepared by filling standard two-piece hard gelatin capsules each with 100 milligrams of powdered active ingredient, 150 milligrams of lactose, 50 milligrams of cellulose, and 6 milligrams magnesium stearate.

Soft Gelatin Capsules

A mixture of active ingredient in a digestable oil such as soybean oil, cottonseed oil or olive oil may be prepared and injected by means of a positive displacement pump into gelatin to form soft gelatin capsules containing 100 milligrams of the active ingredient. The capsules should be washed and dried.

Tablets

Tablets may be prepared by conventional procedures so that the dosage unit is 100 milligrams of active ingredient, 0.2 milligrams of colloidal silicon dioxide, 5 milligrams of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch and 98.8 milligrams of lactose. Appropriate coatings may be applied to increase palatability or delay absorption.

Injectable

A parenteral composition suitable for administration by injection may be prepared by stirring 1.5% by weight of active ingredient in 10% by volume propylene glycol and water. The solution should be made isotonic with sodium chloride and sterilized.

Suspension

An aqueous suspension can be prepared for oral administration so that each 5 mL contain 100 mg of finely divided active ingredient, 200 mg of sodium carboxymethyl cellulose, 5 mg of sodium benzoate, 1.0 g of sorbitol solution, U.S.P., and 0.025 mL of vanillin.

Where the compounds of this invention are combined with other anticoagulant agents, for example, a daily dosage may be about 0.1 to 100 milligrams of the compound of Formula I and about 1 to 7.5 milligrams of the second anticoagulant, per kilogram of patient body weight. For a tablet dosage form, the compounds of this invention generally may be present in an amount of about 5 to 10 milligrams per dosage unit, and the second anti-coagulant in an amount of about 1 to 5 milligrams per dosage unit.

Where the compounds of Formula I are administered in combination with an anti-platelet agent, by way of general guidance, typically a daily dosage may be about 0.01 to 25 milligrams of the compound of Formula I and about 50 to 150 milligrams of the anti-platelet agent, preferably about 0.1 to 1 milligrams of the compound of Formula I and about 1 to 3 milligrams of antiplatelet agents, per kilogram of patient body weight.

Where the compounds of Formula I are adminstered in combination with thrombolytic agent, typically a daily dosage may be about 0.1 to 1 milligrams of the compound of Formula I, per kilogram of patient body weight and, in the case of the thrombolytic agents, the usual dosage of the thrombolyic agent when administered alone may be reduced by about 70-80% when administered with a compound of Formula I.

Where two or more of the foregoing second therapeutic agents are administered with the compound of Formula I, generally the amount of each component in a typical daily dosage and typical dosage form may be reduced relative to the usual dosage of the agent when administered alone, in view of the additive or synergistic effect of the therapeutic agents when administered in combination.

Particularly when provided as a single dosage unit, the potential exists for a chemical interaction between the combined active ingredients. For this reason, when the compound of Formula I and a second therapeutic agent are combined in a single dosage unit they are formulated such that although the active ingredients are combined in a single dosage unit, the physical contact between the active ingredients is minimized (that is, reduced). For example, one active ingredient may be enteric coated. By enteric coating one of the active ingredients, it is possible not only to minimize the contact between the combined active ingredients, but also, it is possible to control the release of one of these components in the gastrointestinal tract such that one of these components is not released in the stomach but rather is released in the intestines. One of the active ingredients may also be coated with a material which effects a sustained-release throughout the gastrointestinal tract and also serves to minimize physical contact between the combined active ingredients. Furthermore, the sustained-released component can be additionally enteric coated such that the release of this component occurs only in the intestine. Still another approach would involve the formulation of a combination product in which the one component is coated with a sustained and/or enteric release polymer, and the other component is also coated with a polymer such as a lowviscosity grade of hydroxypropyl methylcellulose (HPMC) or other appropriate materials as known in the art, in order to further separate the active components. The polymer coating serves to form an additional barrier to interaction with the other component.

These as well as other ways of minimizing contact between the components of combination products of the present invention, whether administered in a single dosage form or administered in separate forms but at the same time by the same manner, will be readily apparent to those skilled in the art, once armed with the present disclosure.

The following tables contain representative examples of the present invention. Each entry in each table is intended to be paired with each formulae at the start of the table. For example, example 1 of Table 1 is intended to be paired with each of the formulae shown in Table 1. Example 1 of Table 2 is intended to be paired with each of the formulae shown in Table 2.

The following nomenclature is intended for group A in the following tables.

TABLE 1

Z is C(O)NH or C(O)CH₂

Ex# R^(1a) A B 1 CH3 phenyl 2-(aminosulfonyl)phenyl 2 CH3 phenyl 2-(methylaminosulfonyl)phenyl 3 CH3 phenyl 1-pyrrolidinocarbonyl 4 CH3 phenyl 2-(methylsulfonyl)phenyl 5 CH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl 6 CH3 phenyl 2-N-pyrrolidinylmethyl)phenyl 7 CH3 phenyl 1-methyl-2-imidazolyl 8 CH3 phenyl 2-methyl-1-imidazolyl 9 CH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 10 CH3 phenyl 2-N-(cyclopropyl- methyl)aminomethyl)phenyl 11 CH3 phenyl 2-N-(cyclobutyl)- aminomethyl)phenyl 12 CH3 phenyl 2-N-(cyclopentyl)- aminomethyl)phenyl 13 CH3 phenyl 2-N-(3-hydroxypyrrolidinyl)- methyl)phenyl 14 CH3 2-pyridyl 2-(aminosulfonyl)phenyl 15 CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 16 CH3 2-pyridyl 1-pyrrolidinocarbonyl 17 CH3 2-pyridyl 2-(methylsulfonyl)phenyl 18 CH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 19 CH3 2-pyridyl 2-N-pyrrolidinylmethyl)phenyl 20 CH3 2-pyridyl 1-methyl-2-imidazolyl 21 CH3 2-pyridyl 2-methyl-1-imidazolyl 22 CH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 23 CH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 24 CH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 25 CH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 26 CH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 27 CH3 3-pyridyl 2-(aminosulfonyl)phenyl 28 CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 29 CH3 3-pyridyl 1-pyrrolidinocarbonyl 30 CH3 3-pyridyl 2-(methylsulfonyl)phenyl 31 CH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 32 CH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 33 CH3 3-pyridyl 1-methyl-2-imidazolyl 34 CH3 3-pyridyl 2-methyl-1-imidazolyl 35 CH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 36 CH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 37 CH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 38 CH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 39 CH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 40 CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 41 CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 42 CH3 2-pyrimidyl 1-pyrrolidinocarbonyl 43 CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 44 CH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 45 CH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 46 CH3 2-pyrimidyl 1-methyl-2-imidazolyl 47 CH3 2-pyrimidyl 2-methyl-1-imidazolyl 48 CH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 49 CH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 50 CH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 51 CH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 52 CH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 53 CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 54 CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 55 CH3 5-pyrimidyl 1-pyrrolidinocarbonyl 56 CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 57 CH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 58 CH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 59 CH3 5-pyrimidyl 1-methyl-2-imidazolyl 60 CH3 5-pyrimidyl 2-methyl-1-imidazolyl 61 CH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 62 CH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 63 CH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 64 CH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 65 CH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 66 CH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl 67 CH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 68 CH3 2-Cl-phenyl 1-pyrrolidinocarbonyl 69 CH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 70 CH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 71 CH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 72 CH3 2-Cl-phenyl 1-methyl-2-imidazolyl 73 CH3 2-Cl-phenyl 2-methyl-1-imidazolyl 74 CH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 75 CH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 76 CH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 77 CH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 78 CH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 79 CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 80 CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 81 CH3 2-F-phenyl 1-pyrrolidinocarbonyl 82 CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 83 CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 84 CH3 2-F-phenyl 2-(N--pyrrolidinylmethyl)phenyl 85 CH3 2-F-phenyl 1-methyl-2-imidazolyl 86 CH3 2-F-phenyl 2-methyl-1-imidazolyl 87 CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 88 CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 89 CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 90 CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 91 CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 92 CH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 93 CH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 94 CH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 95 CH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 96 CH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 97 CH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 98 CH3 2,6-diF-phenyl 1-methyl-2-imidazolyl 99 CH3 2,6-diF-phenyl 2-methyl-1-imidazoly1 100 CH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 101 CH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 102 CH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 103 CH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 104 CH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 105 CH2CH3 phenyl 2-(aminosulfonyl)phenyl 106 CH2CH3 phenyl 2-(methylaminosulfonyl)phenyl 107 CH2CH3 phenyl 1-pyrrolidinocarbonyl 108 CH2CH3 phenyl 2-(methylsulfonyl)phenyl 109 CH2CH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl 110 CH2CH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl 111 CH2CH3 phenyl 1-methyl-2-imidazolyl 112 CH2CH3 phenyl 2-methyl-1-imidazolyl 113 CH2CH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 114 CH2CH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 115 CH2CH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 116 CH2CH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 117 CH2CH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 118 CH2CH3 2-pyridyl 2-(aminosulfonyl)phenyl 119 CH2CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 120 CH2CH3 2-pyridyl 1-pyrrolidinocarbonyl 121 CH2CH3 2-pyridyl 2-(methylsulfonyl)phenyl 122 CH2CH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 123 CH2CH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 124 CH2CH3 2-pyridyl 1-methyl-2-imidazolyl 125 CH2CH3 2-pyridyl 2-methyl-1-imidazolyl 126 CH2CH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 127 CH2CH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 128 CH2CH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 129 CH2CH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 130 CH2CH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 131 CH2CH3 3-pyridyl 2-(aminosulfonyl)phenyl 132 CH2CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 133 CH2CH3 3-pyridyl 1-pyrrolidinocarbonyl 134 CH2CH3 3-pyridyl 2-(methylsulfonyl)phenyl 135 CH2CH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 136 CH2CH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 137 CH2CH3 3-pyridyl 1-methyl-2-imidazolyl 138 CH2CH3 3-pyridyl 2-methyl-1-imidazolyl 139 CH2CH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 140 CH2CH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 141 CH2CH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 142 CH2CH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 143 CH2CH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 144 CH2CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 145 CH2CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 146 CH2CH3 2-pyrimidyl 1-pyrrolidinocarbonyl 147 CH2CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 148 CH2CH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 149 CH2CH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 150 CH2CH3 2-pyrimidyl 1-methyl-2-imidazolyl 151 CH2CH3 2-pyrimidyl 2-methyl-1-imidazolyl 152 CH2CH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 153 CH2CH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 154 CH2CH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 155 CH2CH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 156 CH2CH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 157 CH2CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 158 CH2CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 159 CH2CH3 5-pyrimidyl 1-pyrrolidinocarbonyl 160 CH2CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 161 CH2CH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 162 CH2CH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 163 CH2CH3 5-pyrimidyl 1-methyl-2-imidazolyl 164 CH2CH3 5-pyrimidyl 2-methyl-1-imidazolyl 165 CH2CH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 166 CH2CH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 167 CH2CH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 168 CH2CH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 169 CH2CH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 170 CH2CH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl 171 CH2CH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 172 CH2CH3 2-Cl-phenyl 1-pyrrolidinocarbonyl 173 CH2CH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 174 CH2CH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 175 CH2CH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 176 CH2CH3 2-Cl-phenyl 1-methyl-2-imidazolyl 177 CH2CH3 2-Cl-phenyl 2-methyl-1-imidazolyl 178 CH2CH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 179 CH2CH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 180 CH2CH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 181 CH2CH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 182 CH2CH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 183 CH2CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 184 CH2CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 185 CH2CH3 2-F-phenyl 1-pyrrolidinocarbonyl 186 CH2CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 187 CH2CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 188 CH2CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 189 CH2CH3 2-F-phenyl 1-methyl-2-imidazolyl 190 CH2CH3 2-F-phenyl 2-methyl-1-imidazolyl 191 CH2CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 192 CH2CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 193 CH2CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 194 CH2CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 195 CH2CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 196 CH2CH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 197 CH2CH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 198 CH2CH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 199 CH2CH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 200 CH2CH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 201 CH2CH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 202 CH2CH3 2,6-diF-phenyl 1-methyl-2-imidazolyl 203 CH2CH3 2,6-diF-phenyl 2-methyl-1-imidazolyl 204 CH2CH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 205 CH2CH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 206 CH2CH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 207 CH2CH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 208 CH2CH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 209 CF3 phenyl 2-(aminosulfonyl)phenyl 210 CF3 phenyl 2-(methylaminosulfonyl)phenyl 211 CF3 phenyl 1-pyrrolidinocarbonyl 212 CF3 phenyl 2-(methylsulfonyl)phenyl 213 CF3 phenyl 2-(N,N- dimethylaminomethyl)phenyl 214 CF3 phenyl 2-(N-pyrrolidinylmethyl)phenyl 215 CF3 phenyl 1-methyl-2-imidazolyl 216 CF3 phenyl 2-methyl-1-imidazolyl 217 CF3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 218 CF3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 219 CF3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 220 CF3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 221 CF3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 222 CF3 2-pyridyl 2-(aminosulfonyl)phenyl 223 CF3 2-pyridyl 2-(methylaminosulfonyl)phenyl 224 CF3 2-pyridyl 1-pyrrolidinocarbonyl 225 CF3 2-pyridyl 2-(methylsulfonyl)phenyl 226 CF3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 227 CF3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 228 CF3 2-pyridyl 1-methyl-2-imidazolyl 229 CF3 2-pyridyl 2-methyl-1-imidazolyl 230 CF3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 231 CF3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 232 CF3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 233 CF3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 234 CF3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 235 CF3 3-pyridyl 2-(aminosulfonyl)phenyl 236 CF3 3-pyridyl 2-(methylaminosulfonyl)phenyl 237 CF3 3-pyridyl 1-pyrrolidinocarbonyl 238 CF3 3-pyridyl 2-(methylsulfonyl)phenyl 239 CF3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 240 CF3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 241 CF3 3-pyridyl 2-(N-methyl-2-imidazolyl 242 CF3 3-pyridyl 2-methyl-1-imidazolyl 243 CF3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 244 CF3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 245 CF3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 246 CF3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 247 CF3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 248 CF3 2-pyrimidyl 2-(aminosulfonyl)phenyl 249 CF3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 250 CF3 2-pyrimidyl 1-pyrrolidinocarbonyl 251 CF3 2-pyrimidyl 2-(methylsulfonyl)phenyl 252 CF3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 253 CF3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 254 CF3 2-pyrimidyl 1-methyl-2-imidazolyl 255 CF3 2-pyrimidyl 2-methyl-1-imidazolyl 256 CF3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 257 CF3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 258 CF3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 259 CF3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 260 CF3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 261 CF3 5-pyrimidyl 2-(aminosulfonyl)phenyl 262 CF3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 263 CF3 5-pyrimidyl 1-pyrrolidinocarbonyl 264 CF3 5-pyrimidyl 2-(methylsulfonyl)phenyl 265 CF3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 266 CF3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 267 CF3 5-pyrimidyl 1-methyl-2-imidazolyl 268 CF3 5-pyrimidyl 2-methyl-1-imidazolyl 269 CF3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 270 CF3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 271 CF3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 272 CF3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 273 CF3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 274 CF3 2-Cl-phenyl 2-(aminosulfonyl)phenyl 275 CF3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 276 CF3 2-Cl-phenyl 1-pyrrolidinocarbonyl 277 CF3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 278 CF3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 279 CF3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 280 CF3 2-Cl-phenyl 1-methyl-2-imidazolyl 281 CF3 2-Cl-phenyl 2-methyl-1-imidazolyl 282 CF3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 283 CF3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 284 CF3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 285 CF3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 286 CF3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 287 CF3 2-F-phenyl 2-(aminosulfonyl)phenyl 288 CF3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 289 CF3 2-F-phenyl 1-pyrrolidinocarbonyl 290 CF3 2-F-phenyl 2-(methylsulfonyl)phenyl 291 CF3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 292 CF3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 293 CF3 2-F-phenyl 1-methyl-2-imidazolyl 294 CF3 2-F-phenyl 2-methyl-1-imidazolyl 295 CF3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 296 CF3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 297 CF3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 298 CF3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 299 CF3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 300 CF3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 301 CF3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 302 CF3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 303 CF3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 304 CF3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 305 CF3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 306 CF3 2,6-diF-phenyl 1-methyl-2-imidazolyl 307 CF3 2,6-diF-phenyl 2-methyl-1-imidazolyl 308 CF3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 309 CF3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 310 CF3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 311 CF3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 312 CF3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 313 SCH3 phenyl 2-(aminosulfonyl)phenyl 314 SCH3 phenyl 2-(methylaminosulfonyl)phenyl 315 SCH3 phenyl 1-pyrrolidinocarbonyl 316 SCH3 phenyl 2-(methylsulfonyl)phenyl 317 SCH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl 318 SCH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl 319 SCH3 phenyl 1-methyl-2-imidazolyl 320 SCH3 phenyl 2-methyl-1-imidazolyl 321 SCH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 322 SCH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 323 SCH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 324 SCH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 325 SCH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 326 SCH3 2-pyridyl 2-(aminosulfonyl)phenyl 327 SCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 328 SCH3 2-pyridyl 1-pyrrolidinocarbonyl 329 SCH3 2-pyridyl 2-(methylsulfonyl)phenyl 330 SCH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 331 SCH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 332 SCH3 2-pyridyl 1-methyl-2-imidazolyl 333 SCH3 2-pyridyl 2-methyl-1-imidazolyl 334 SCH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 335 SCH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 336 SCH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 337 SCH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 338 SCH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 339 SCH3 3-pyridyl 2-(aminosulfonyl)phenyl 340 SCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 341 SCH3 3-pyridyl 1-pyrrolidinocarbonyl 342 SCH3 3-pyridyl 2-(methylsulfonyl)phenyl 343 SCH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 344 SCH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 345 SCH3 3-pyridyl 1-methyl-2-imidazolyl 346 SCH3 3-pyridyl 2-methyl-1-imidazolyl 347 SCH3 3-pyridyi 2-(dimethylaminomethyl)-1- imidazolyl 348 SCH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 349 SCH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 350 SCH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 351 SCH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 352 SCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 353 SCH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 354 SCH3 2-pyrimidyl 1-pyrrolidinocarbonyl 355 SCH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 356 SCH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 357 SCH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 358 SCH3 2-pyrimidyl 1-methyl-2-imidazolyl 359 SCH3 2-pyrimidyl 2-methyl-1-imidazolyl 360 SCH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 361 SCH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 362 SCH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 363 SCH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 364 SCH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 365 SCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 366 SCH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 367 SCH3 5-pyrimidyl 1-pyrrolidinocarbonyl 368 SCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 369 SCH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 370 SCH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 371 SCH3 5-pyrimidyl 1-methyl-2-imidazolyl 372 SCH3 5-pyrimidyl 2-methyl-1-imidazolyl 373 SCH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 374 SCH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 375 SCH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 376 SCH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 377 SCH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 378 SCH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl 379 SCH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 380 SCH3 2-Cl-phenyl 1-pyrrolidinocarbonyl 381 SCH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 382 SCH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 383 SCH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 384 SCH3 2-Cl-phenyl 1-methyl-2-imidazolyl 385 SCH3 2-Cl-phenyl 2-methyl-1-imidazolyl 386 SCH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 387 SCH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 388 SCH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 389 SCH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 390 SCH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 391 SCH3 2-F-phenyl 2-(aminosulfonyl)phenyl 392 SCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 393 SCH3 2-F-phenyl 1-pyrrolidinocarbonyl 394 SCH3 2-F-phenyl 2-(methylsulfonyl)phenyl 395 SCH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 396 SCH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 397 SCH3 2-F-phenyl 1-methyl-2-imidazolyl 398 SCH3 2-F-phenyl 2-methyl-1-imidazolyl 399 SCH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 400 SCH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 401 SCH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 402 SCH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 403 SCH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 404 SCH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 405 SCH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 406 SCH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 407 SCH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 408 SCH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 409 SCH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 410 SCH3 2,6-diF-phenyl 1-methyl-2-imidazolyl 411 SCH3 2,6-diF-phenyl 2-methyl-1-imidazolyl 412 SCH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 413 SCH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 414 SCH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 415 SCH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 416 SCH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 417 SOCH3 phenyl 2-(aminosulfonyl)phenyl 418 SOCH3 phenyl 2-(methylaminosulfonyl)phenyl 419 SOCH3 phenyl 1-pyrrolidinocarbonyl 420 SOCH3 phenyl 2-(methylsulfonyl)phenyl 421 SOCH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl 422 SOCH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl 423 SOCH3 phenyl 1-methyl-2-imidazolyl 424 SOCH3 phenyl 2-methyl-1-imidazolyl 425 SOCH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 426 SOCH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 427 SOCH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 428 SOCH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 429 SOCH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 430 SOCH3 2-pyridyl 2-(aminosulfonyl)phenyl 431 SOCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 432 SOCH3 2-pyridyl 1-pyrrolidinocarbonyl 433 SOCH3 2-pyridyl 2-(methylsulfonyl)phenyl 434 SOCH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 435 SOCH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 436 SOCH3 2-pyridyl 1-methyl-2-imidazolyl 437 SOCH3 2-pyridyl 2-methyl-1-imidazolyl 438 SOCH3 2-pyridyl 2-(N-dimethylaminomethyl)-1- imidazolyl 439 SOCH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 440 SOCH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 441 SOCH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 442 SOCH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 443 SOCH3 3-pyridyl 2-(aminosulfonyl)phenyl 444 SOCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 445 SOCH3 3-pyridyl 1-pyrrolidinocarbonyl 446 SOCH3 3-pyridyl 2-(methylsulfonyl)phenyl 447 SOCH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 448 SOCH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 449 SOCH3 3-pyridyl 1-methyl-2-imidazolyl 450 SOCH3 3-pyridyl 2-methyl-1-imidazolyl 451 SOCH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 452 SOCH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 453 SOCH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 454 SOCH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 455 SOCH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 456 SOCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 457 SOCH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 458 SOCH3 2-pyrimidyl 1-pyrrolidinocarbonyl 459 SOCH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 460 SOCH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 461 SOCH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 462 SOCH3 2-pyrimidyl 1-methyl-2-imidazolyl 463 SOCH3 2-pyrimidyl 2-methyl-1-imidazolyl 464 SOCH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 465 SOCH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 466 SOCH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 467 SOCH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 468 SOCH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 469 SOCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 470 SOCH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 471 SOCH3 5-pyrimidyl 1-pyrrolidinocarbonyl 472 SOCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 473 SOCH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 474 SOCH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 475 SOCH3 5-pyrimidyl 1-methyl-2-imidazolyl 476 SOCH3 5-pyrimidyl 2-methyl-1-imidazolyl 477 SOCH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 478 SOCH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 479 SOCH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 480 SOCH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 481 SOCH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 482 SOCH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl 483 SOCH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 484 SOCH3 2-Cl-phenyl 1-pyrrolidinocarbonyl 485 SOCH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 486 SOCH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 487 SOCH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 488 SOCH3 2-Cl-phenyl 1-methyl-2-imidazolyl 489 SOCH3 2-Cl-phenyl 2-methyl-1-imidazolyl 490 SOCH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 491 SOCH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 492 SOCH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 493 SOCH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 494 SOCH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 495 SOCH3 2-F-phenyl 2-(aminosulfonyl)phenyl 496 SOCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 497 SOCH3 2-F-phenyl 1-pyrrolidinocarbonyl 498 SOCH3 2-F-phenyl 2-(methylsulfonyl)phenyl 499 SOCH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 500 SOCH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 501 SOCH3 2-F-phenyl 1-methyl-2-imidazolyl 502 SOCH3 2-F-phenyl 2-methyl-1-imidazolyl 503 SOCH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 504 SOCH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 505 SOCH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 506 SOCH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 507 SOCH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 508 SOCH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 509 SOCH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 510 SOCH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 511 SOCH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 512 SOCH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 513 SOCH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 514 SOCH3 2,6-diF-phenyl 1-methyl-2-imidazolyl 515 SOCH3 2,6-diF-phenyl 2-methyl-1-imidazolyl 516 SOCH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 517 SOCH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 518 SOCH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 519 SOCH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 520 SOCH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 521 SO2CH3 phenyl 2-(aminosulfonyl)phenyl 522 SO2CH3 phenyl 2-(methylaminosulfonyl)phenyl 523 SO2CH3 phenyl 1-pyrrolidinocarbonyl 524 SO2CH3 phenyl 2-(methylsulfonyl)phenyl 525 SO2CH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl 526 SO2CH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl 527 SO2CH3 phenyl 1-methyl-2-imidazolyl 528 SO2CH3 phenyl 2-methyl-1-imidazolyl 529 SO2CH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 530 SO2CH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 531 SO2CH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 532 SO2CH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 533 SO2CH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 534 SO2CH3 2-pyridyl 2-(aminosulfonyl)phenyl 535 SO2CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 536 SO2CH3 2-pyridyl 1-pyrrolidinocarbonyl 537 SO2CH3 2-pyridyl 2-(methylsulfonyl)phenyl 538 SO2CH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 539 SO2CH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 540 SO2CH3 2-pyridyl 1-methyl-2-imidazolyl 541 SO2CH3 2-pyridyl 2-methyl-1-imidazolyl 542 SO2CH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 543 SO2CH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 544 SO2CH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 545 SO2CH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 546 SO2CH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 547 SO2CH3 3-pyridyl 2-(aminosulfonyl)phenyl 548 SO2CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 549 SO2CH3 3-pyridyl 1-pyrrolidinocarbonyl 550 SO2CH3 3-pyridyl 2-(methylsulfonyl)phenyl 551 SO2CH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 552 SO2CH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 553 SO2CH3 3-pyridyl 1-methyl-2-imidazolyl 554 SO2CH3 3-pyridyl 2-methyl-1-imidazolyl 555 SO2CH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 556 SO2CH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 557 SO2CH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 558 SO2CH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 559 SO2CH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 560 SO2CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 561 SO2CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 562 SO2CH3 2-pyrimidyl 1-pyrrolidinocarbonyl 563 SO2CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 564 SO2CH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 565 SO2CH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 566 SO2CH3 2-pyrimidyl 1-methyl-2-imidazolyl 567 SO2CH3 2-pyrimidyl 2-methyl-1-imidazolyl 568 SO2CH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 569 SO2CH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 570 SO2CH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 571 SO2CH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 572 SO2CH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 573 SO2CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 574 SO2CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 575 SO2CH3 5-pyrimidyl 1-pyrrolidinocarbonyl 576 SO2CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 577 SO2CH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 578 SO2CH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 579 SO2CH3 5-pyrimidyl 1-methyl-2-imidazolyl 580 SO2CH3 5-pyrimidyl 2-methyl-1-imidazolyl 581 SO2CH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 582 SO2CH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 583 SO2CH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 584 SO2CH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 585 SO2CH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 586 SO2CH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl 587 SO2CH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 588 SO2CH3 2-Cl-phenyl 1-pyrrolidinocarbonyl 589 SO2CH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 590 SO2CH3 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 591 SO2CH3 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 592 SO2CH3 2-Cl-phenyl 1-methyl-2-imidazolyl 593 SO2CH3 2-Cl-phenyl 2-methyl-1-imidazolyl 594 SO2CH3 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 595 SO2CH3 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 596 SO2CH3 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 597 SO2CH3 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 598 SO2CH3 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 599 SO2CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 600 SO2CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 601 SO2CH3 2-F-phenyl 1-pyrrolidinocarbonyl 602 SO2CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 603 SO2CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 604 SO2CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 605 SO2CH3 2-F-phenyl 1-methyl-2-imidazolyl 606 SO2CH3 2-F-phenyl 2-methyl-1-imidazolyl 607 SO2CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 608 SO2CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 609 SO2CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 610 SO2CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 611 SO2CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 612 SO2CH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 613 SO2CH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 614 SO2CH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 615 SO2CH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 616 SO2CH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 617 SO2CH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 618 SO2CH3 2,6-diF-phenyl 1-methyl-2-imidazolyl 619 SO2CH3 2,6-diF-phenyl 2-methyl-1-imidazolyl 620 SO2CH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 621 SO2CH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 622 SO2CH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 623 SO2CH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 624 SO2CH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 625 Cl phenyl 2-(aminosulfonyl)phenyl 626 Cl phenyl 2-(methylaminosulfonyl)phenyl 627 Cl phenyl 1-pyrrolidinocarbonyl 628 Cl phenyl 2-(methylsulfonyl)phenyl 629 Cl phenyl 2-(N,N- dimethylaminomethyl)phenyl 630 Cl phenyl 2-(N-pyrrolidinylmethyl)phenyl 631 Cl phenyl 1-methyl-2-imidazolyl 632 Cl phenyl 2-methyl-1-imidazolyl 633 Cl phenyl 2-(dimethylaminomethyl)-1- imidazolyl 634 Cl phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 635 Cl phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 636 Cl phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 637 Cl phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 638 Cl 2-pyridyl 2-(aminosulfonyl)phenyl 639 Cl 2-pyridyl 2-(methylaminosulfonyl)phenyl 640 Cl 2-pyridyl 1-pyrrolidinocarbonyl 641 Cl 2-pyridyl 2-(methylsulfonyl)phenyl 642 Cl 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 643 Cl 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 644 Cl 2-pyridyl 1-methyl-2-imidazolyl 645 Cl 2-pyridyl 2-methyl-1-imidazolyl 646 Cl 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 647 Cl 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 648 Cl 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 649 Cl 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 650 Cl 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 651 Cl 3-pyridyl 2-(aminosulfonyl)phenyl 652 Cl 3-pyridyl 2-(methylaminosulfonyl)phenyl 653 Cl 3-pyridyl 1-pyrrolidinocarbonyl 654 Cl 3-pyridyl 2-(methylsulfonyl)phenyl 655 Cl 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 656 Cl 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 657 Cl 3-pyridyl 1-methyl-2-imidazolyl 658 Cl 3-pyridyl 2-methyl-1-imidazolyl 659 Cl 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 660 Cl 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 661 Cl 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 662 Cl 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 663 Cl 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 664 Cl 2-pyrimidyl 2-(aminosulfonyl)phenyl 665 Cl 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 666 Cl 2-pyrimidyl 1-pyrrolidinocarbonyl 667 Cl 2-pyrimidyl 2-(methylsulfonyl)phenyl 668 Cl 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 669 Cl 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 670 Cl 2-pyrimidyl 1-methyl-2-imidazolyl 671 Cl 2-pyrimidyl 2-methyl-1-imidazolyl 672 Cl 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 673 Cl 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 674 Cl 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 675 Cl 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 676 Cl 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 677 Cl 5-pyrimidyl 2-(aminosulfonyl)phenyl 678 Cl 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 679 Cl 5-pyrimidyl 1-pyrrolidinocarbonyl 680 Cl 5-pyrimidyl 2-(methylsulfonyl)phenyl 681 Cl 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 682 Cl 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 683 Cl 5-pyrimidyl 1-methyl-2-imidazolyl 684 Cl 5-pyrimidyl 2-methyl-1-imidazolyl 685 Cl 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 686 Cl 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 687 Cl 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 688 Cl 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 689 Cl 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 690 Cl 2-Cl-phenyl 2-(aminosulfonyl)phenyl 691 Cl 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 692 Cl 2-Cl-phenyl 1-pyrrolidinocarbonyl 693 Cl 2-Cl-phenyl 2-(methylsulfonyl)phenyl 694 Cl 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 695 Cl 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 696 Cl 2-Cl-phenyl 1-methyl-2-imidazolyl 697 Cl 2-Cl-phenyl 2-methyl-1-imidazolyl 698 Cl 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 699 Cl 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 700 Cl 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 701 Cl 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 702 Cl 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 703 Cl 2-F-phenyl 2-(aminosulfonyl)phenyl 704 Cl 2-F-phenyl 2-(methylaminosulfonyl)phenyl 705 Cl 2-F-phenyl 1-pyrrolidinocarbonyl 706 Cl 2-F-phenyl 2-(methylsulfonyl)phenyl 707 Cl 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 708 Cl 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 709 Cl 2-F-phenyl 1-methyl-2-imidazolyl 710 Cl 2-F-phenyl 2-methyl-1-imidazolyl 711 Cl 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 712 Cl 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 713 Cl 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 714 Cl 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 715 Cl 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 716 Cl 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 717 Cl 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 718 Cl 2,6-diF-phenyl 1-pyrrolidinocarbonyl 719 Cl 2,6-diF-phenyl 2-(methoxysulfonyl)phenyl 720 Cl 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 721 Cl 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 722 Cl 2,6-diF-phenyl 1-methyl-2-imidazolyl 723 Cl 2,6-diF-phenyl 2-methyl-1-imidazolyl 724 Cl 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 725 Cl 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 726 Cl 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 727 Cl 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 728 Cl 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 729 F phenyl 2-(aminosulfonyl)phenyl 730 F phenyl 2-(methylaminosulfonyl)phenyl 731 F phenyl 1-pyrrolidinocarbonyl 732 F phenyl 2-(methylsulfonyl)phenyl 733 F phenyl 2-(N,N- dimethylaminomethyl)phenyl 734 F phenyl 2-(N-pyrrolidinylmethyl)phenyl 735 F phenyl 1-methyl-2-imidazolyl 736 F phenyl 2-methyl-1-imidazolyl 737 F phenyl 2-(dimethylaminomethyl)-1- imidazolyl 738 F phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 739 F phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 740 F phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 741 F phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 742 F 2-pyridyl 2-(aminosulfonyl)phenyl 743 F 2-pyridyl 2-(methylaminosulfonyl)phenyl 744 F 2-pyridyl 1-pyrrolidinocarbonyl 745 F 2-pyridyl 2-(methylsulfonyl)phenyl 746 F 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 747 F 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 748 F 2-pyridyl 1-methyl-2-imidazolyl 749 F 2-pyridyl 2-methyl-1-imidazolyl 750 F 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 751 F 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 752 F 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 753 F 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 754 F 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 755 F 3-pyridyl 2-(aminosulfonyl)phenyl 756 F 3-pyridyl 2-(methylaminosulfonyl)phenyl 757 F 3-pyridyl 1-pyrrolidinocarbonyl 758 F 3-pyridyl 2-(methylsulfonyl)phenyl 759 F 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 760 F 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 761 F 3-pyridyl 1-methyl-2-imidazolyl 762 F 3-pyridyl 2-methyl-1-imidazolyl 763 F 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 764 F 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 765 F 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 766 F 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 767 F 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 768 F 2-pyrimidyl 2-(aminosulfonyl)phenyl 769 F 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 770 F 2-pyrimidyl 1-pyrrolidinocarbonyl 771 F 2-pyrimidyl 2-(methylsulfonyl)phenyl 772 F 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 773 F 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 774 F 2-pyrimidyl 1-methyl-2-imidazolyl 775 F 2-pyrimidyl 2-methyl-1-imidazolyl 776 F 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 777 F 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 778 F 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 779 F 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 780 F 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 781 F 5-pyrimidyl 2-(aminosulfonyl)phenyl 782 F 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 783 F 5-pyrimidyl 1-pyrrolidinocarbonyl 784 F 5-pyrimidyl 2-(methylsulfonyl)phenyl 785 F 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 786 F 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 787 F 5-pyrimidyl 1-methyl-2-imidazolyl 788 F 5-pyrimidyl 2-methyl-1-imidazolyl 789 F 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 790 F 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 791 F 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 792 F 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 793 F 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 794 F 2-F-phenyl 2-(aminosulfonyl)phenyl 795 F 2-F-phenyl 2-(methylaminosulfonyl)phenyl 796 F 2-F-phenyl 1-pyrrolidinocarbonyl 797 F 2-F-phenyl 2-(methylsulfonyl)phenyl 798 F 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 799 F 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 800 F 2-F-phenyl 1-methyl-2-imidazolyl 801 F 2-F-phenyl 2-methyl-1-imidazolyl 802 F 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 803 F 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 804 F 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 805 F 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 806 F 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 807 F 2-F-phenyl 2-(aminosulfonyl)phenyl 808 F 2-F-phenyl 2-(methylaminosulfonyl)phenyl 809 F 2-F-phenyl 1-pyrrolidinocarbonyl 810 F 2-F-phenyl 2-(methylsulfonyl)phenyl 811 F 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 812 F 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 813 F 2-F-phenyl 1-methyl-2-imidazolyl 814 F 2-F-phenyl 2-methyl-1-imidazolyl 815 F 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 816 F 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 817 F 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 818 F 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 819 F 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 820 F 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 821 F 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 822 F 2,6-diF-phenyl 1-pyrrolidinocarbonyl 823 F 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 824 F 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 825 F 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 826 F 2,6-diF-phenyl 1-methyl-2-imidazolyl 827 F 2,6-diF-phenyl 2-methyl-1-imidazolyl 828 F 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 829 F 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 830 F 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 831 F 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 832 F 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 833 CO2CH3 phenyl 2-(aminosulfonyl)phenyl 834 CO2CH3 phenyl 2-(methylaminosulfonyl)phenyl 835 CO2CH3 phenyl 1-pyrrolidinocarbonyl 836 CO2CH3 phenyl 2-(methylsulfonyl)phenyl 837 CO2CH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl 838 CO2CH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl 839 CO2CH3 phenyl 1-methyl-2-imidazolyl 840 CO2CH3 phenyl 2-methyl-1-imidazolyl 841 CO2CH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 842 CO2CH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 843 CO2CH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 844 CO2CH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 845 CO2CH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 846 CO2CH3 2-pyridyl 2-(aminosulfonyl)phenyl 847 CO2CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 848 CO2CH3 2-pyridyl 1-pyrrolidinocarbonyl 849 CO2CH3 2-pyridyl 2-(methylsulfonyl)phenyl 850 CO2CH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 851 CO2CH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 852 CO2CH3 2-pyridyl 1-methyl-2-imidazolyl 853 CO2CH3 2-pyridyl 2-methyl-1-imidazolyl 854 CO2CH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 855 CO2CH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 856 CO2CH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 857 CO2CH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 858 CO2CH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 859 CO2CH3 3-pyridyl 2-(aminosulfonyl)phenyl 860 CO2CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 861 CO2CH3 3-pyridyl 1-pyrrolidinocarbonyl 862 CO2CH3 3-pyridyl 2-(methylsulfonyl)phenyl 863 CO2CH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 864 CO2CH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 865 CO2CH3 3-pyridyl 1-methyl-2-imidazolyl 866 CO2CH3 3-pyridyl 2-methyl-1-imidazolyl 867 CO2CH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 868 CO2CH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 869 CO2CH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 870 CO2CH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 871 CO2CH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 872 CO2CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 873 CO2CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 874 CO2CH3 2-pyrimidyl 1-pyrrolidinocarbonyl 875 CO2CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 876 CO2CH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 877 CO2CH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 878 CO2CH3 2-pyrimidyl 1-methyl-2-imidazolyl 879 CO2CH3 2-pyrimidyl 2-methyl-1-imidazolyl 880 CO2CH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 881 CO2CH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 882 CO2CH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 883 CO2CH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 884 CO2CH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 885 CO2CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 886 CO2CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 887 CO2CH3 5-pyrimidyl 1-pyrrolidinocarbonyl 888 CO2CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 889 CO2CH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 890 CO2CH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 891 CO2CH3 5-pyrimidyl 1-methyl-2-imidazolyl 892 CO2CH3 5-pyrimidyl 2-methyl-1-imidazolyl 893 CO2CH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 894 CO2CH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 895 CO2CH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 896 CO2CH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 897 CO2CH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 898 CO2CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 899 CO2CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 900 CO2CH3 2-F-phenyl 1-pyrrolidinocarbonyl 901 CO2CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 902 CO2CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 903 CO2CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 904 CO2CH3 2-F-phenyl 1-methyl-2-imidazolyl 905 CO2CH3 2-F-phenyl 2-methyl-1-imidazolyl 906 CO2CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 907 CO2CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 908 CO2CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 909 CO2CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 910 CO2CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 911 CO2CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 912 CO2CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 913 CO2CH3 2-F-phenyl 1-pyrrolidinocarbonyl 914 CO2CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 915 CO2CH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 916 CO2CH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 917 CO2CH3 2-F-phenyl 1-methyl-2-imidazolyl 918 CO2CH3 2-F-phenyl 2-methyl-1-imidazolyl 919 CO2CH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 920 CO2CH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 921 CO2CH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 922 CO2CH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 923 CO2CH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 924 CO2CH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 925 CO2CH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 926 CO2CH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 927 CO2CH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 928 CO2CH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 929 CO2CH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 930 CO2CH3 2,6-diF-phenyl 1-methyl-2-imidazolyl 931 CO2CH3 2,6-diF-phenyl 2-methyl-1-imidazolyl 932 CO2CH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 933 CO2CH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 934 CO2CH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 935 CO2CH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 936 CO2CH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 937 CH2OCH3 phenyl 2-(aminosulfonyl)phenyl 938 CH2OCH3 phenyl 2-(methylaminosulfonyl)phenyl 939 CH2OCH3 phenyl 1-pyrrolidinocarbonyl 940 CH2OCH3 phenyl 2-(methylsulfonyl)phenyl 941 CH2OCH3 phenyl 2-(N,N- dimethylaminomethyl)phenyl 942 CH2OCH3 phenyl 2-(N-pyrrolidinylmethyl)phenyl 943 CH2OCH3 phenyl 1-methyl-2-imidazolyl 944 CH2OCH3 phenyl 2-methyl-1-imidazolyl 945 CH2OCH3 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 946 CH2OCH3 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 947 CH2OCH3 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 948 CH2OCH3 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 949 CH2OCH3 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 950 CH2OCH3 2-pyridyl 2-(aminosulfonyl)phenyl 951 CH2OCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 952 CH2OCH3 2-pyridyl 1-pyrrolidinocarbonyl 953 CH2OCH3 2-pyridyl 2-(methylsulfonyl)phenyl 954 CH2OCH3 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 955 CH2OCH3 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 956 CH2OCH3 2-pyridyl 1-methyl-2-imidazolyl 957 CH2OCH3 2-pyridyl 2-methyl-1-imidazolyl 958 CH2OCH3 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 959 CH2OCH3 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 960 CH2OCH3 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 961 CH2OCH3 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 962 CH2OCH3 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 963 CH2OCH3 3-pyridyl 2-(aminosulfonyl)phenyl 964 CH2OCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 965 CH2OCH3 3-pyridyl 1-pyrrolidinocarbonyl 966 CH2OCH3 3-pyridyl 2-(methylsulfonyl)phenyl 967 CH2OCH3 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 968 CH2OCH3 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 969 CH2OCH3 3-pyridyl 1-methyl-2-imidazolyl 970 CH2OCH3 3-pyridyl 2-methyl-1-imidazolyl 971 CH2OCH3 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 972 CH2OCH3 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 973 CH2OCH3 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 974 CH2OCH3 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 975 CH2OCH3 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 976 CH2OCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 977 CH2OCH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 978 CH2OCH3 2-pyrimidyl 1-pyrrolidinocarbonyl 979 CH2OCH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 980 CH2OCH3 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 981 CH2OCH3 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 982 CH2OCH3 2-pyrimidyl 1-methyl-2-imidazolyl 983 CH2OCH3 2-pyrimidyl 2-methyl-1-imidazolyl 984 CH2OCH3 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 985 CH2OCH3 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 986 CH2OCH3 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 987 CH2OCH3 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 988 CH2OCH3 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 989 CH2OCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 990 CH2OCH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 991 CH2OCH3 5-pyrimidyl 1-pyrrolidinocarbonyl 992 CH2OCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 993 CH2OCH3 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 994 CH2OCH3 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 995 CH2OCH3 5-pyrimidyl 1-methyl-2-imidazolyl 996 CH2OCH3 5-pyrimidyl 2-methyl-1-imidazolyl 997 CH2OCH3 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 998 CH2OCH3 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 999 CH2OCH3 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1000 CH2OCH3 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1001 CH2OCH3 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1002 CH2OCH3 2-F-phenyl 2-(aminosulfonyl)phenyl 1003 CH2OCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1004 CH2OCH3 2-F-phenyl 1-pyrrolidinocarbonyl 1005 CH2OCH3 2-F-phenyl 2-(methylsulfonyl)phenyl 1006 CH2OCH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1007 CH2OCH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1008 CH2OCH3 2-F-phenyl 1-methyl-2-imidazolyl 1009 CH2OCH3 2-F-phenyl 2-methyl-1-imidazolyl 1010 CH2OCH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1011 CH2OCH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1012 CH2OCH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1013 CH2OCH3 2-F-phenyl 2-(N-cyclopentyl)- aminomethyl)phenyl 1014 CH2OCH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1015 CH2OCH3 2-F-phenyl 2-(aminosulfonyl)phenyl 1016 CH2OCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1017 CH2OCH3 2-F-phenyl 1-pyrrolidinocarbonyl 1018 CH2OCH3 2-F-phenyl 2-(methylsulfonyl)phenyl 1019 CH2OCH3 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1020 CH2OCH3 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1021 CH2OCH3 2-F-phenyl 1-methyl-2-imidazolyl 1022 CH2OCH3 2-F-phenyl 2-methyl-1-imidazolyl 1023 CH2OCH3 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1024 CH2OCH3 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1025 CH2OCH3 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1026 CH2OCH3 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1027 CH2OCH3 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1028 CH2OCH3 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 1029 CH2OCH3 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 1030 CH2OCH3 2,6-diF-phenyl 1-pyrrolidinocarbonyl 1031 CH2OCH3 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 1032 CH2OCH3 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1033 CH2OCH3 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1034 CH2OCH3 2,6-diF-phenyl 1-methyl-2-imidazolyl 1035 CH2OCH3 2,6-diF-phenyl 2-methyl-1-imidazolyl 1036 CH2OCH3 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1037 CH2OCH3 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1038 CH2OCH3 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1039 CH2OCH3 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1040 CH2OCH3 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1041 CONH2 phenyl 2-(aminosulfonyl)phenyl 1042 CONH2 phenyl 2-(methylaminosulfonyl)phenyl 1043 CONH2 phenyl 1-pyrrolidinocarbonyl 1044 CONH2 phenyl 2-(methylsulfonyl)phenyl 1045 CONH2 phenyl 2-(N,N- dimethylaminomethyl)phenyl 1046 CONH2 phenyl 2-(N-pyrrolidinylmethyl)phenyl 1047 CONH2 phenyl 1-methyl-2-imidazolyl 1048 CONH2 phenyl 2-methyl-1-imidazolyl 1049 CONH2 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1050 CONH2 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1051 CONH2 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1052 CONH2 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1053 CONH2 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1054 CONH2 2-pyridyl 2-(aminosulfonyl)phenyl 1055 CONH2 2-pyridyl 2-(methylaminosulfonyl)phenyl 1056 CONH2 2-pyridyl 1-pyrrolidinocarbonyl 1057 CONH2 2-pyridyl 2-(methylsulfonyl)phenyl 1058 CONH2 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1059 CONH2 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1060 CONH2 2-pyridyl 1-methyl-2-imidazolyl 1061 CONH2 2-pyridyl 2-methyl-1-imidazolyl 1062 CONH2 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1063 CONH2 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1064 CONH2 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1065 CONH2 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1066 CONH2 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1067 CONH2 3-pyridyl 2-(aminosulfonyl)phenyl 1068 CONH2 3-pyridyl 2-(methylaminosulfonyl)phenyl 1069 CONH2 3-pyridyl 1-pyrrolidinocarbonyl 1070 CONH2 3-pyridyl 2-(methylsulfonyl)phenyl 1071 CONH2 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1072 CONH2 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1073 CONH2 3-pyridyl 1-methyl-2-imidazolyl 1074 CONH2 3-pyridyl 2-methyl-1-imidazolyl 1075 CONH2 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1076 CONH2 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1077 CONH2 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1078 CONH2 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1079 CONH2 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1080 CONH2 2-pyrimidyl 2-(aminosulfonyl)phenyl 1081 CONH2 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1082 CONH2 2-pyrimidyl 1-pyrrolidinocarbonyl 1083 CONH2 2-pyrimidyl 2-(methylsulfonyl)phenyl 1084 CONH2 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1085 CONH2 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1086 CONH2 2-pyrimidyl 1-methyl-2-imidazolyl 1087 CONH2 2-pyrimidyl 2-methyl-1-imidazolyl 1088 CONH2 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1089 CONH2 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1090 CONH2 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1091 CONH2 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1092 CONH2 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1093 CONH2 5-pyrimidyl 2-(aminosulfonyl)phenyl 1094 CONH2 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 1095 CONH2 5-pyrimidyl 1-pyrrolidinocarbonyl 1096 CONH2 5-pyrimidyl 2-(methylsulfonyl)phenyl 1097 CONH2 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1098 CONH2 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1099 CONH2 5-pyrimidyl 1-methyl-2-imidazolyl 1100 CONH2 5-pyrimidyl 2-methyl-1-imidazolyl 1101 CONH2 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1102 CONH2 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1103 CONH2 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1104 CONH2 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1105 CONH2 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1106 CONH2 2-F-phenyl 2-(aminosulfonyl)phenyl 1107 CONH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1108 CONH2 2-F-phenyl 1-pyrrolidinocarbonyl 1109 CONH2 2-F-phenyl 2-(methylsulfonyl)phenyl 1110 CONH2 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1111 CONH2 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1112 CONH2 2-F-phenyl 1-methyl-2-imidazolyl 1113 CONH2 2-F-phenyl 2-methyl-1-imidazolyl 1114 CONH2 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1115 CONH2 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1116 CONH2 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1117 CONH2 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1118 CONH2 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1119 CONH2 2-F-phenyl 2-(aminosulfonyl)phenyl 1120 CONH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1121 CONH2 2-F-phenyl 1-pyrrolidinocarbonyl 1122 CONH2 2-F-phenyl 2-(methylsulfonyl)phenyl 1123 CONH2 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1124 CONH2 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1125 CONH2 2-F-phenyl 1-methyl-2-imidazolyl 1126 CONH2 2-F-phenyl 2-methyl-1-imidazolyl 1127 CONH2 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1128 CONH2 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1129 CONH2 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1130 CONH2 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1131 CONH2 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1132 CONH2 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 1133 CONH2 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 1134 CONH2 2,6-diF-phenyl 1-pyrrolidinocarbonyl 1135 CONH2 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 1136 CONH2 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1137 CONH2 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1138 CONH2 2,6-diF-phenyl 1-methyl-2-imidazolyl 1139 CONH2 2,6-diF-phenyl 2-methyl-1-imidazolyl 1140 CONH2 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1141 CONH2 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1142 CONH2 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1143 CONH2 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1144 CONH2 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1145 CN phenyl 2-(aminosulfonyl)phenyl 1146 CN phenyl 2-(methylaminosulfonyl)phenyl 1147 CN phenyl 1-pyrrolidinocarbonyl 1148 CN phenyl 2-(methylsulfonyl)phenyl 1149 CN phenyl 2-(N,N- dimethylaminomethyl)phenyl 1150 CN phenyl 2-(N-pyrrolidinylmethyl)phenyl 1151 CN phenyl 1-methyl-2-imidazolyl 1152 CN phenyl 2-methyl-1-imidazolyl 1153 CN phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1154 CN phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1155 CN phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1156 CN phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1157 CN phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1158 CN 2-pyridyl 2-(aminosulfonyl)phenyl 1159 CN 2-pyridyl 2-(methylaminosulfonyl)phenyl 1160 CN 2-pyridyl 1-pyrrolidinocarbonyl 1161 CN 2-pyridyl 2-(methylsulfonyl)phenyl 1162 CN 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1163 CN 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1164 CN 2-pyridyl 1-methyl-2-imidazolyl 1165 CN 2-pyridyl 2-methyl-1-imidazolyl 1166 CN 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1167 CN 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1168 CN 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1169 CN 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1170 CN 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1171 CN 3-pyridyl 2-(aminosulfonyl)phenyl 1172 CN 3-pyridyl 2-(methylaminosulfonyl)phenyl 1173 CN 3-pyridyl 1-pyrrolidinocarbonyl 1174 CN 3-pyridyl 2-(methylsulfonyl)phenyl 1175 CN 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1176 CN 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1177 CN 3-pyridyl 1-methyl-2-imidazolyl 1178 CN 3-pyridyl 2-methyl-1-imidazolyl 1179 CN 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1180 CN 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1181 CN 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1182 CN 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1183 CN 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1184 CN 2-pyrimidyl 2-(aminosulfonyl)phenyl 1185 CN 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1186 CN 2-pyrimidyl 1-pyrrolidinocarbonyl 1187 CN 2-pyrimidyl 2-(methylsulfonyl)phenyl 1188 CN 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1189 CN 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1190 CN 2-pyrimidyl 1-methyl-2-imidazolyl 1191 CN 2-pyrimidyl 2-methyl-1-imidazolyl 1192 CN 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1193 CN 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1194 CN 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1195 CN 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1196 CN 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1197 CN 5-pyrimidyl 2-(aminosulfonyl)phenyl 1198 CN 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 1199 CN 5-pyrimidyl 1-pyrrolidinocarbonyl 1200 CN 5-pyrimidyl 2-(methylsulfonyl)phenyl 1201 CN 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1202 CN 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1203 CN 5-pyrimidyl 1-methyl-2-imidazolyl 1204 CN 5-pyrimidyl 2-methyl-1-imidazolyl 1205 CN 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1206 CN 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1207 CN 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1208 CN 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1209 CN 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1210 CN 2-F-phenyl 2-(aminosulfonyl)phenyl 1211 CN 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1212 CN 2-F-phenyl 1-pyrrolidinocarbonyl 1213 CN 2-F-phenyl 2-(methylsulfonyl)phenyl 1214 CN 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1215 CN 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1216 CN 2-F-phenyl 1-methyl-2-imidazolyl 1217 CN 2-F-phenyl 2-methyl-1-imidazolyl 1218 CN 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1219 CN 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1220 CN 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1221 CN 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1222 CN 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1223 CN 2-F-phenyl 2-(aminosulfonyl)phenyl 1224 CN 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1225 CN 2-F-phenyl 1-pyrrolidinocarbonyl 1226 CN 2-F-phenyl 2-(methylsulfonyl)phenyl 1227 CN 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1228 CN 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1229 CN 2-F-phenyl 1-methyl-2-imidazolyl 1230 CN 2-F-phenyl 2-methyl-1-imidazolyl 1231 CN 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1232 CN 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1233 CN 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1234 CN 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1235 CN 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1236 CN 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 1237 CN 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 1238 CN 2,6-diF-phenyl 1-pyrrolidinocarbonyl 1239 CN 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 1240 CN 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1241 CN 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1242 CN 2,6-diF-phenyl 1-methyl-2-imidazolyl 1243 CN 2,6-diF-phenyl 2-methyl-1-imidazolyl 1244 CN 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1245 CN 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1246 CN 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1247 CN 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1248 CN 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1249 CH2NH2 phenyl 2-(aminosulfonyl)phenyl 1250 CH2NH2 phenyl 2-(methylaminosulfonyl)phenyl 1251 CH2NH2 phenyl 1-pyrrolidinocarbonyl 1252 CH2NH2 phenyl 2-(methylsulfonyl)phenyl 1253 CH2NH2 phenyl 2-(N,N- dimethylaminomethyl)phenyl 1254 CH2NH2 phenyl 2-(N-pyrrolidinylmethyl)phenyl 1255 CH2NH2 phenyl 1-methyl-2-imidazolyl 1256 CH2NH2 phenyl 2-methyl-1-imidazolyl 1257 CH2NH2 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1258 CH2NH2 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1259 CH2NH2 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1260 CH2NH2 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1261 CH2NH2 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1262 CH2NH2 2-pyridyl 2-(aminosulfonyl)phenyl 1263 CH2NH2 2-pyridyl 2-(methylaminosulfonyl)phenyl 1264 CH2NH2 2-pyridyl 1-pyrrolidinocarbonyl 1265 CH2NH2 2-pyridyl 2-(methylsulfonyl)phenyl 1266 CH2NH2 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1267 CH2NH2 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1268 CH2NH2 2-pyridyl 1-methyl-2-imidazolyl 1269 CH2NH2 2-pyridyl 2-methyl-1-imidazolyl 1270 CH2NH2 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1271 CH2NH2 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1272 CH2NH2 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1273 CH2NH2 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1274 CH2NH2 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1275 CH2NH2 3-pyridyl 2-(aminosulfonyl)phenyl 1276 CH2NH2 3-pyridyl 2-(methylaminosulfonyl)phenyl 1277 CH2NH2 3-pyridyl 1-pyrrolidinocarbonyl 1278 CH2NH2 3-pyridyl 2-(methylsulfonyl)phenyl 1279 CH2NH2 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 1280 CH2NH2 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 1281 CH2NH2 3-pyridyl 1-methyl-2-imidazolyl 1282 CH2NH2 3-pyridyl 2-methyl-1-imidazolyl 1283 CH2NH2 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 1284 CH2NH2 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1285 CH2NH2 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1286 CH2NH2 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1287 CH2NH2 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1288 CH2NH2 2-pyrimidyl 2-(aminosulfonyl)phenyl 1289 CH2NH2 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1290 CH2NH2 2-pyrimidyl 1-pyrrolidinocarbonyl 1291 CH2NH2 2-pyrimidyl 2-(methylsulfonyl)phenyl 1292 CH2NH2 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1293 CH2NH2 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1294 CH2NH2 2-pyrimidyl 1-methyl-2-imidazolyl 1295 CH2NH2 2-pyrimidyl 2-methyl-1-imidazolyl 1296 CH2NH2 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1297 CH2NH2 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1298 CH2NH2 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1299 CH2NH2 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1300 CH2NH2 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1301 CH2NH2 5-pyrimidyl 2-(aminosulfonyl)phenyl 1302 CH2NH2 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 1303 CH2NH2 5-pyrimidyl 1-pyrrolidinocarbonyl 1304 CH2NH2 5-pyrimidyl 2-(methylsulfonyl)phenyl 1305 CH2NH2 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 1306 CH2NH2 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 1307 CH2NH2 5-pyrimidyl 1-methyl-2-imidazolyl 1308 CH2NH2 5-pyrimidyl 2-methyl-1-imidazolyl 1309 CH2NH2 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 1310 CH2NH2 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1311 CH2NH2 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1312 CH2NH2 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1313 CH2NH2 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1314 CH2NH2 2-F-phenyl 2-(aminosulfonyl)phenyl 1315 CH2NH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1316 CH2NH2 2-F-phenyl 1-pyrrolidinocarbonyl 1317 CH2NH2 2-F-phenyl 2-(methylsulfonyl)phenyl 1318 CH2NH2 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1319 CH2NH2 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1320 CH2NH2 2-F-phenyl 1-methyl-2-imidazolyl 1321 CH2NH2 2-F-phenyl 2-methyl-1-imidazolyl 1322 CH2NH2 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1323 CH2NH2 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1324 CH2NH2 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1325 CH2NH2 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1326 CH2NH2 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1327 CH2NH2 2-F-phenyl 2-(aminosulfonyl)phenyl 1328 CH2NH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1329 CH2NH2 2-F-phenyl 1-pyrrolidinocarbonyl 1330 CH2NH2 2-F-phenyl 2-(methylsulfonyl)phenyl 1331 CH2NH2 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1332 CH2NH2 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1333 CH2NH2 2-F-phenyl 1-methyl-2-imidazolyl 1334 CH2NH2 2-F-phenyl 2-methyl-1-imidazolyl 1335 CH2NH2 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1336 CH2NH2 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1337 CH2NH2 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1338 CH2NH2 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1339 CH2NH2 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1340 CH2NH2 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 1341 CH2NH2 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 1342 CH2NH2 2,6-diF-phenyl 1-pyrrolidinocarbonyl 1343 CH2NH2 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 1344 CH2NH2 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 1345 CH2NH2 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 1346 CH2NH2 2,6-diF-phenyl 1-methyl-2-imidazolyl 1347 CH2NH2 2,6-diF-phenyl 2-methyl-1-imidazolyl 1348 CH2NH2 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 1349 CH2NH2 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 1350 CH2NH2 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 1351 CH2NH2 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 1352 CH2NH2 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 1353 CH2NH- phenyl 2-(aminosulfonyl)phenyl SO2CH3 1354 CH2NH- phenyl 2-(methylaminosulfonyl)phenyl SO2CH3 1355 CH2NH- phenyl 1-pyrrolidinocarbonyl SO2CH3 1356 CH2NH- phenyl 2-(methylsulfonyl)phenyl SO2CH3 1357 CH2NH- phenyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1358 CH2NH- phenyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1359 CH2NH- phenyl 1-methyl-2-imidazolyl SO2CH3 1360 CH2NH- phenyl 2-methyl-1-imidazolyl SO2CH3 1361 CH2NH- phenyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1362 CH2NH- phenyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1363 CH2NH- phenyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1364 CH2NH- phenyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1365 CH2NH- phenyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1366 CH2NH- 2-pyridyl 2-(aminosulfonyl)phenyl SO2CH3 1367 CH2NH- 2-pyridyl 2-(methylaminosulfonyl)phenyl SO2CH3 1368 CH2NH- 2-pyridyl 1-pyrrolidinocarbonyl SO2CH3 1369 CH2NH- 2-pyridyl 2-(methylsulfonyl)phenyl SO2CH3 1370 CH2NH- 2-pyridyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl SO2CH3 1371 CH2NH- 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1372 CH2NH- 2-pyridyl 1-methyl-2-imidazolyl SO2CH3 1373 CH2NH- 2-pyridyl 2-methyl-1-imidazolyl SO2CH3 1374 CH2NH- 2-pyridyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1375 CH2NH- 2-pyridyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1376 CH2NH- 2-pyridyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1377 CH2NH- 2-pyridyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1378 CH2NH- 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1379 CH2NH- 3-pyridyl 2-(aminosulfonyl)phenyl SO2CH3 1380 CH2NH- 3-pyridyl 2-(methylaminosulfonyl)phenyl SO2CH3 1381 CH2NH- 3-pyridyl 1-pyrrolidinocarbonyl SO2CH3 1382 CH2NH- 3-pyridyl 2-(methylsulfonyl)phenyl SO2CH3 1383 CH2NH- 3-pyridyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1384 CH2NH- 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1385 CH2NH- 3-pyridyl 1-methyl-2-imidazolyl SO2CH3 1386 CH2NH- 3-pyridyl 2-methyl-1-imidazolyl SO2CH3 1387 CH2NH- 3-pyridyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1388 CH2NH- 3-pyridyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1389 CH2NH- 3-pyridyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1390 CH2NH- 3-pyridyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1391 CH2NH- 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1392 CH2NH- 2-pyrimidyl 2-(aminosulfonyl)phenyl SO2CH3 1393 CH2NH- 2-pyrimidyl 2-(methylaminosulfonyl)phenyl SO2CH3 1394 CH2NH- 2-pyrimidyl 1-pyrrolidinocarbonyl SO2CH3 1395 CH2NH- 2-pyrimidyl 2-(methylsulfonyl)phenyl SO2CH3 1396 CH2NH- 2-pyrimidyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1397 CH2NH- 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1398 CH2NH- 2-pyrimidyl 1-methyl-2-imidazolyl SO2CH3 1399 CH2NH- 2-pyrimidyl 2-methyl-1-imidazolyl SO2CH3 1400 CH2NH- 2-pyrimidyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1401 CH2NH- 2-pyrimidyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1402 CH2NH- 2-pyrimidyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1403 CH2NH- 2-pyrimidyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1404 CH2NH- 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1405 CH2NH- 5-pyrimidyl 2-(aminosulfonyl)phenyl SO2CH3 1406 CH2NH- 5-pyrimidyl 2-(methylaminosulfonyl)phenyl SO2CH3 1407 CH2NH- 5-pyrimidyl 1-pyrrolidinocarbonyl SO2CH3 1408 CH2NH- 5-pyrimidyl 2-(methylsulfonyl)phenyl SO2CH3 1409 CH2NH- 5-pyrimidyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1410 CH2NH- 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1411 CH2NH- 5-pyrimidyl 1-methyl-2-imidazolyl SO2CH3 1412 CH2NH- 5-pyrimidyl 2-methyl-1-imidazolyl SO2CH3 1413 CH2NH- 5-pyrimidyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1414 CH2NH- 5-pyrimidyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1415 CH2NH- 5-pyrimidyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1416 CH2NH- 5-pyrimidyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1417 CH2NH- 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1418 CH2NH- 2-Cl-phenyl 2-(aminosulfonyl)phenyl SO2CH3 1419 CH2NH- 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl SO2CH3 1420 CH2NH- 2-Cl-phenyl 1-pyrrolidinocarbonyl SO2CH3 1421 CH2NH- 2-Cl-phenyl 2-(methylsulfonyl)phenyl SO2CH3 1422 CH2NH- 2-Cl-phenyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1423 CH2NH- 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1424 CH2NH- 2-Cl-phenyl 1-methyl-2-imidazolyl SO2CH3 1425 CH2NH- 2-Cl-phenyl 2-methyl-1-imidazolyl SO2CH3 1426 CH2NH- 2-Cl-phenyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1427 CH2NH- 2-Cl-phenyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1428 CH2NH- 2-Cl-phenyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1429 CH2NH- 2-Cl-phenyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1430 CH2NH- 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1431 CH2NH- 2-F-phenyl 2-(aminosulfonyl)phenyl SO2CH3 1432 CH2NH- 2-F-phenyl 2-(methylaminosulfonyl)phenyl SO2CH3 1433 CH2NH- 2-F-phenyl 1-pyrrolidinocarbonyl SO2CH3 1434 CH2NH- 2-F-phenyl 3-(methylsulfonyl)phenyl SO2CH3 1435 CH2NH- 2-F-phenyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1436 CH2NH- 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1437 CH2NH- 2-F-phenyl 1-methyl-2-imidazolyl SO2CH3 1438 CH2NH- 2-F-phenyl 2-methyl-1-imidazolyl SO2CH3 1439 CH2NH- 2-F-phenyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1440 CH2NH- 2-F-phenyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1441 CH2NH- 2-F-phenyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1442 CH2NH- 2-F-phenyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1443 CH2NH- 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl 1444 CH2NH- 2,6-diF-phenyl 2-(aminosulfonyl)phenyl SO2CH3 1445 CH2NH- 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl SO2CH3 1446 CH2NH- 2,6-diF-phenyl 1-pyrrolidinocarbonyl SO2CH3 1447 CH2NH- 2,6-diF-phenyl 2-(methylsulfonyl)phenyl SO2CH3 1448 CH2NH- 2,6-diF-phenyl 2-(N,N- SO2CH3 dimethylaminomethyl)phenyl 1449 CH2NH- 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl SO2CH3 1450 CH2NH- 2,6-diF-phenyl 1-methyl-2-imidazolyl SO2CH3 1451 CH2NH- 2,6-diF-phenyl 2-methyl-1-imidazolyl SO2CH3 1452 CH2NH- 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- SO2CH3 imidazolyl 1453 CH2NH- 2,6-diF-phenyl 2-(N-(cyclopropyl- SO2CH3 methyl)aminomethyl)phenyl 1454 CH2NH- 2,6-diF-phenyl 2-(N-(cyclobutyl)- SO2CH3 aminomethyl)phenyl 1455 CH2NH- 2,6-diF-phenyl 2-(N-(cyclopentyl)- SO2CH3 aminomethyl)phenyl 1456 CH2NH- 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- SO2CH3 methyl)phenyl

TABLE 2

Z is C(O)NH or C(O)CH₂

Ex # A B 1 phenyl 2-(aminosulfonyl)phenyl 2 phenyl 2-(methylaminosulfonyl)phenyl 3 phenyl 1-pyrrolidinocarbonyl 4 phenyl 2-(methylsulfonyl)phenyl 5 phenyl 2-(N,N- dimethylaminomethyl)phenyl 6 phenyl 2-(N-pyrrolidinylmethyl)phenyl 7 phenyl 1-methyl-2-imidazolyl 8 phenyl 2-methyl-1-imidazolyl 9 phenyl 2-(dimethylaminomethyl)-1- imidazolyl 10 phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 11 phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 12 phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 13 phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 14 2-pyridyl 2-(aminosulfonyl)phenyl 15 2-pyridyl 2-(methylaminosulfonyl)phenyl 16 2-pyridyl 1-pyrrolidinocarbonyl 17 2-pyridyl 2-(methylsulfonyl)phenyl 18 2-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 19 2-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 20 2-pyridyl 1-methyl-2-imidazolyl 21 2-pyridyl 2-methyl-1-imidazolyl 22 2-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 23 2-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 24 2-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 25 2-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 26 2-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 27 3-pyridyl 2-(aminosulfonyl)phenyl 28 3-pyridyl 2-(methylaminosulfonyl)phenyl 29 3-pyridyl 1-pyrrolidinocarbonyl 30 3-pyridyl 2-(methylsulfonyl)phenyl 31 3-pyridyl 2-(N,N- dimethylaminomethyl)phenyl 32 3-pyridyl 2-(N-pyrrolidinylmethyl)phenyl 33 3-pyridyl 1-methyl-2-imidazolyl 34 3-pyridyl 2-methyl-1-imidazolyl 35 3-pyridyl 2-(dimethylaminomethyl)-1- imidazolyl 36 3-pyridyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 37 3-pyridyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 38 3-pyridyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 39 3-pyridyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 40 2-pyrimidyl 2-(aminosulfonyl)phenyl 41 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 42 2-pyrimidyl 1-pyrrolidinocarbonyl 43 2-pyrimidyl 2-(methylsulfonyl)phenyl 44 2-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 45 2-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 46 2-pyrimidyl 1-methyl-2-imidazolyl 47 2-pyrimidyl 2-methyl-1-imidazolyl 48 2-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 49 2-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 50 2-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 51 2-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 52 2-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 53 5-pyrimidyl 2-(aminosulfonyl)phenyl 54 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 55 5-pyrimidyl 1-pyrrolidinocarbonyl 56 5-pyrimidyl 2-(methylsulfonyl)phenyl 57 5-pyrimidyl 2-(N,N- dimethylaminomethyl)phenyl 58 5-pyrimidyl 2-(N-pyrrolidinylmethyl)phenyl 59 5-pyrimidyl 1-methyl-2-imidazolyl 60 5-pyrimidyl 2-methyl-1-imidazolyl 61 5-pyrimidyl 2-(dimethylaminomethyl)-1- imidazolyl 62 5-pyrimidyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 63 5-pyrimidyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 64 5-pyrimidyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 65 5-pyrimidyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 66 2-Cl-phenyl 2-(aminosulfonyl)phenyl 67 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 68 2-Cl-phenyl 1-pyrrolidinocarbonyl 69 2-Cl-phenyl 2-(methylsulfonyl)phenyl 70 2-Cl-phenyl 2-(N,N- dimethylaminomethyl)phenyl 71 2-Cl-phenyl 2-(N-pyrrolidinylmethyl)phenyl 72 2-Cl-phenyl 1-methyl-2-imidazolyl 73 2-Cl-phenyl 2-methyl-1-imidazolyl 74 2-Cl-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 75 2-Cl-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 76 2-Cl-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 77 2-Cl-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 78 2-Cl-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 79 2-F-phenyl 2-(aminosulfonyl)phenyl 80 2-F-phenyl 2-(methylaminosulfonyl)phenyl 81 2-F-phenyl 1-pyrrolidinocarbonyl 82 2-F-phenyl 2-(methylsulfonyl)phenyl 83 2-F-phenyl 2-(N,N- dimethylaminomethyl)phenyl 84 2-F-phenyl 2-(N-pyrrolidinylmethyl)phenyl 85 2-F-phenyl 1-methyl-2-imidazolyl 86 2-F-phenyl 2-methyl-1-imidazolyl 87 2-F-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 88 2-F-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 89 2-F-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 90 2-F-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 91 2-F-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl 92 2,6-diF-phenyl 2-(aminosulfonyl)phenyl 93 2,6-diF-phenyl 2-(methylaminosulfonyl)phenyl 94 2,6-diF-phenyl 1-pyrrolidinocarbonyl 95 2,6-diF-phenyl 2-(methylsulfonyl)phenyl 96 2,6-diF-phenyl 2-(N,N- dimethylaminomethyl)phenyl 97 2,6-diF-phenyl 2-(N-pyrrolidinylmethyl)phenyl 98 2,6-diF-phenyl 1-methyl-2-imidazolyl 99 2,6-diF-phenyl 2-methyl-1-imidazolyl 100 2,6-diF-phenyl 2-(dimethylaminomethyl)-1- imidazolyl 101 2,6-diF-phenyl 2-(N-(cyclopropyl- methyl)aminomethyl)phenyl 102 2,6-diF-phenyl 2-(N-(cyclobutyl)- aminomethyl)phenyl 103 2,6-diF-phenyl 2-(N-(cyclopentyl)- aminomethyl)phenyl 104 2,6-diF-phenyl 2-(N-(3-hydroxypyrrolidinyl)- methyl)phenyl

Obviously, numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise that as specifically described herein. 

What is claimed is:
 1. A compound of formula I:

ring D is selected from —(CH₂)₃—, —CH₂CH═CH—, —CH₂N═CH—, and a 5 membered aromatic system containing from 0-1 N; ring D is substituted with 0-2 R, provided that when ring D is unsubstituted, it contains at least one heteroatom; E is pyridyl substituted with 0-1 R; R is selected from Cl, F, Br, I, OH, C₁₋₃ alkoxy, NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂, CH₂CH₂NH₂, CH₂CH₂NH(C₁₋₃ alkyl), and CH₂CH₂N(C₁₋₃ alkyl)₂; M is selected from the group:

J is O or S; J^(a) is NH or NR^(1a); Z is selected from (CR⁸R⁹)₁₋₄, (CR⁸R⁹)_(r)O(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)O(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)OC(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)C(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³C(O)(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)OC(O)O(CR⁸R⁹)_(r), (CH₂)_(r)OC(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³C(O)O(CR⁸R⁹)_(r), (CH₂)_(r)NR³C(O)NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)S(O)_(p)(CR⁸R⁹)_(r), (CCR⁸R⁹)_(r)SO₂NR³(CR⁸R⁹)_(r), (CR⁸R⁹)_(r)NR³SO₂(CR⁸R⁹)_(r), and (CR⁸R⁹)_(r)NR³SO₂NR³(CR⁸R⁹)_(r), provided that Z does not form a N—N, N—O, N—S, NCH₂N, NCH₂O, or NCH₂S bond with the groups to which Z is attached; R^(1a) is selected from H, —(CH₂)_(r)—R^(1′), —CH═CH—R^(1′), NHCH₂R^(1″), OCH₂R^(1″), SCH₂R^(1″), NH(CH₂)₂(CH₂)_(t)R^(1′), O(CH₂)₂(CH₂)_(t)R^(1′), and S(CH₂)₂(CH₂)_(t)R^(1′); R^(1′) is selected from H, C₁₋₃ alkyl, F, Cl, Br, I, —CN, —CHO, (CF₂)_(r)CF₃, (CH₂)_(r)OR², NR²R^(2a), C(O)R^(2c), OC(O)R², (CF₂)_(r)CO₂R^(2c), S(O)_(p)R^(2b), NR²(CH₂)_(r)OR², C(═NR^(2c))NR²R^(2a), NR²C(O)R^(2b), NR²C(O)NHR^(2b), NR²C(O)₂R^(2a), OC(O)NR^(2a)R^(2b), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR², SO₂NR²R^(2a), NR²SO₂R^(2b), C₃₋₆ carbocycle substituted with 0-2 R⁴, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R⁴; R^(1″) is selected from H, CH(CH₂OR²)₂, C(O)R^(2c), C(O)NR²R^(2a), S(O)R^(2b), S(O)₂R^(2b), and SO₂NR²R^(2a); R², at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b); R^(2a), at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl, benzyl, C₃₋₆ cycloalkylmethyl substituted with 0-2 R^(4b), C₃₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b); R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxy, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b); R^(2c), at each occurrence, is selected from CF₃, OH, C₁₋₄ alkoxy, C₁₋₆ alkyl, benzyl, C₃₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4b); alternatively, R² and R^(2a) combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R^(4b) which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; alternatively, R² and R^(2a), together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R^(4b) and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R³, at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl; R^(3a), at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl; R^(3b), at each occurrence, is selected from H, C₁₋₄ alkyl, and phenyl; R^(3c), at each occurrence, is selected from C₁₋₄ alkyl, and phenyl; A is selected from: C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R⁴; B is selected from: X-Y, NR²R^(2a), C(═NR²)NR²R^(2a), NR²C(═NR²)NR²R^(2a), C₃₋₁₀ carbocycle substituted with 0-2 R^(4a), and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a); X is selected from C₁₋₄ alkylene, —CR²(CR²R^(2b))(CH₂)_(t)—, —C(O)—, —C(═NR^(1″))—, —CR²(NR^(1″)R²)—, —CR² (OR²)—, —CR²(SR²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —S(O)_(p)—, —S(O)_(p)CR²R^(2a)—, —CR²R^(2a)S(O)_(p)—, —S(O)₂NR²—, —NR²S(O)₂—, —NR²S(O)₂CR²R^(2a)—, —CR²R^(2a)S(O)₂NR²—, —NR²S(O)₂NR²—, —C(O)NR²—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—, —CR²R^(2a)NR²C(O)—, —NR²C(O)O—, —OC(O)NR²—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—; Y is selected from: (CH₂)_(r)NR²R^(2a), provided that X-Y do not form a N—N, O—N, or S—N bond, C₃₋₁₀ carbocycle substituted with 0-2 R^(4a), and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a); R⁴, at each occurrence, is selected from H, ═O, (CH₂)_(r)OR², F, Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), NR²C(O)NR²R^(2a), C(═NR²)NR²R^(2a), C(═NS(O)₂R⁵)NR²R^(2a), NHC(═NR²)NR²R^(2a), C(O)NHC(═NR²)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂—C₁₋₄ alkyl, NR²SO₂R⁵, S(O)_(p)R⁵, (CF₂)_(r)CF₃, NHCH₂R^(1″), OCH₂R^(1″), SCH₂R^(1″), N(CH₂)₂(CH₂)_(t)R^(1′), O(CH₂)₂(CH₂)_(t)R^(1′), and S(CH₂)₂(CH₂)_(t)R^(1′), alternatively, one R⁴ is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S; R^(4a), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR², (CH₂)_(r)—F, (CH₂)_(r)—Br, (CH₂)_(r)—Cl, Cl, Br, F, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R²C, NR²C(O)R^(2b), C(O)NR²R^(2a), C(O)NH(CH₂)₂NR²R^(2a), NR²C(O)NR²R^(2a), C(═NR²)NR²R^(2a), NHC(═NR²)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂—C₁₋₄ alkyl, C(O)NHSO₂—C₁₋₄ alkyl, NR²SO₂R⁵, S(O)_(p)R⁵, and (CF₂)_(r)CF₃; alternatively, one R^(4a) is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-1 R⁵; R^(4b), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR³, F, Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, (CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³, (CH₂)_(r)C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), NR³C(O)NR³R^(3a), C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂— phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, and (CF₂)_(r)CF₃; R⁵, at each occurrence, is selected from CF₃, C₁₋₆ alkyl, phenyl substituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶; R⁶, at each occurrence, is selected from H, OH, (CH₂)_(r)OR², halo, C₁₋₄ alkyl, CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2b), NR²C(O)R^(2b), NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a), NR²SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl; R⁷, at each occurrence, is selected from H, OH, C₁₋₆ alkyl, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxy, C₁₋₄ alkoxycarbonyl, (CH₂)_(n)-phenyl, C₆₋₁₀ aryloxy, C₆₋₁₀ aryloxycarbonyl, C₆₋₁₀ arylmethylcarbonyl, C₁₋₄ alkylcarbonyloxy C₁₋₄ alkoxycarbonyl, C₆₋₁₀ arylcarbonyloxy C₁₋₄ alkoxycarbonyl, C₁₋₆ alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C₁₋₄ alkoxycarbonyl; R⁸, at each occurrence, is selected from H, C₁₋₆ alkyl and (CH₂)_(n)-phenyl; alternatively, R⁷ and R⁸ combine to form a 5 or 6 membered saturated, ring which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R⁹, at each occurrence, is selected from H, C₁₋₆ alkyl and (CH₂)_(n)-phenyl; n, at each occurrence, is selected from 0, 1, 2, and 3; m, at each occurrence, is selected from 0, 1, and 2; p, at each occurrence, is selected from 0, 1, and 2; r, at each occurrence, is selected from 0, 1, 2, and 3; s, at each occurrence, is selected from 0, 1, and 2; and, t, at each occurrence, is selected from 0, 1, 2, and
 3. 2. A compound according to claim 1, wherein the compound is selected from the group:

wherein, M is selected from the group:

R is selected from H, Cl, F, Br, I, (CH₂)_(t)OR³, C₁₋₄ alkyl, OCF₃, CF₃, C(O)NR⁷R⁸, and (CR⁸R⁹)_(t)NR⁷R⁸; Z is selected from CH₂O, OCH₂, CH₂NH, NHCH₂, C(O), CH₂C(O), C(O)CH₂, NHC(O), C(O)NH, CH₂S(O)₂, S(O)₂(CH₂), SO₂NH, and NHSO₂, provided that Z does not form a N—N, N—O, NCH₂N, or NCH₂O bond with ring M or group A; A is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R⁴; phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl; B is selected from: H, Y, and X-Y; X is selected from C₁₋₄ alkylene, —C(O)—, —C(═NR)—, —CR²(NR²R^(2a))—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —C(O)NR²—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—, —CR²R^(2a)NR²C(O)—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—; Y is NR²R^(2a) or CH₂NR²R^(2a), provided that X-Y do not form a N—N or O—N bond; alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R^(4a); cylcopropyl, cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl; alternatively, Y is selected from the following bicyclic heteroaryl ring systems:

K is selected from O, S, NH, and N.
 3. A compound according to claim 2, wherein the compound is selected from the group:

M is selected from the group:

Z is C(O)CH₂ and CONH, provided that Z does not form a N—N bond with group A; A is selected from phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2 R⁴; and, B is selected from Y, X-Y, phenyl, pyrrolidino, morpholino, 1,2,3-triazolyl, and imidazolyl, and is substituted with 0-1 R^(4a); B is selected from: Y and X-Y; X is selected from CH₂, —C(O)—, and O; Y is NR²R^(2a) or CH₂NR²R^(2a), provided that X-Y does not form an O—N bond; alternatively, Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R^(4a); phenyl, piperazinyl, pyridyl, pyrimidyl, morpholinyl, pyrrolidinyl, imidazolyl, and 1,2,3-triazolyl; R², at each occurrence, is selected from H, CF₃, CH₃, benzyl, and phenyl; R^(2a), at each occurrence, is selected from H, CF₃, CH₃, CH(CH₃)₂, cyclopropylmethyl, benzyl, and phenyl; alternatively, R² and R^(2a) combine to form a ring system substituted with 0-2 R^(4b), the ring system being selected from pyrrolidinyl, piperazinyl and morpholino; R⁴, at each occurrence, is selected from OH, (CH₂)_(r)OR², Cl, F, C₁₋₄ alkyl, (CH₂)_(r)NR²R^(2a), and (CF₂)_(r)CF₃; R^(4a) is selected from Cl, F, C₁₋₄ alkyl, CF₃, (CH₂)_(r)NR²R^(2a), S(O)_(p)R⁵, SO₂NR²R^(2a), and 1-CF₃-tetrazol-2-yl; R^(4b), at each occurrence, is selected from OH, Cl, F, CH₃, and CF₃; R⁵, at each occurrence, is selected from CF₃, C₁₋₆ alkyl, phenyl, and benzyl; R⁷, at each occurrence, is selected from H, CH₃, and CH₂CH₃; and, R⁸, at each occurrence, is selected from H and CH₃.
 4. A compound according to claim 3, wherein: M is selected from the group:

J is N; R^(1a) is absent or is —(CH₂)_(r)—R^(1′); R^(1′) is selected from H, C₁₋₃ alkyl, F, Cl, —CN, CF₃, (CH₂)_(r)OR², NR²R^(2a), C(O)R^(2c), OC(O)R², S(O)_(p)R^(2b), NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a), C₃₋₆ carbocycle substituted with 0-2 R^(4a), and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R^(4a); A is selected from the group: phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl; and, B is selected from the group: 2-CF₃-phenyl, 2-(aminosulfonyl)phenyl, 2-(methylaminosulfonyl)phenyl, 2-(dimethylaminosulfonyl)phenyl, 1-pyrrolidinocarbonyl, 2-(methylsulfonyl)phenyl, 2-(N,N-dimethylaminomethyl)phenyl, 2-(isopropylaminomethyl)phenyl, 2-(cyclopropylaminomethyl)phenyl, 2-(N-pyrrolidinylmethyl)phenyl, 2-(3-hydroxy-N-pyrrolidinylmethyl)phenyl, 4-morpholino, 2-(1′-CF₃-tetrazol-2-yl)phenyl, 4-morpholinocarbonyl, 1-methyl-2-imidazolyl, 2-methyl-1-imidazolyl, 5-methyl-1-imidazolyl, 2-(N,N-dimethylaminomethyl)imidazolyl, 2-methylsulfonyl-1-imidazolyl and, 5-methyl-1,2,3-triazolyl.
 5. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
 6. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 2 or a pharmaceutically acceptable salt thereof.
 7. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 3 or a pharmaceutically acceptable salt thereof.
 8. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 4 or a pharmaceutically acceptable salt thereof.
 9. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
 10. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 2 or a pharmaceutically acceptable salt thereof.
 11. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 3 or a pharmaceutically acceptable salt thereof.
 12. A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 4 or a pharmaceutically acceptable salt thereof.
 13. A compound according to Table 1 or
 2. 